Mechanisms of Endogenous Nitrosation

  • Steven R. Tannenbaum

Abstract

Substantial evidence has been assembled suggesting the possible health risk from exposure to N-nitroso compounds. Sander1 originally proposed the concept of endogenous intragastric nitrosation, a process capable of generating carcinogenic N-nitroso compounds in humans. It has also been demonstrated that N-nitroso compounds are formed endogenously in animals given nitrite and a suitable amine2,3. However, the initial research on endogenous synthesis of N-nitroso compounds in humans was complicated by the presence of numerous artifacts of the analytical methods and the collection procedures. A method proposed by Ohshima and Bartsch4 was the first potentially suitable procedure for estimating daily human exposure to endogenously formed N-nitroso compounds. The monitoring of urinary levels of N-nitrosoproline (NPRO) after dosing with nitrate and proline was utilized in a human volunteer without adverse biological effects. Since this publication, a number of other investigators have used this procedure to demonstrate the endogenous formation of nitrosoproline as well as other nitrosoamino acids in humans.

Keywords

Ascorbic Acid Methyl Oleate Coeliac Disease Pernicious Anemia Cancer Etiology 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    J. Sander, Kann nittit in der menschlichen Nahrung Ursache einer Krebsentstehung durch Nitrosaminbildung sein? Arch. Hyg. Bakteriol. 151:22 (1967).PubMedGoogle Scholar
  2. 2.
    M. Greenblatt and S. S. Mirvish, Dose-response studies with concurrent administration of piperazine and sodium nitrite to strain A mice, J. Natl. Cancer Inst. 50:119 (1973).PubMedGoogle Scholar
  3. 3.
    W. Lijinsky and H. W. Taylor, Feeding tests in rats on mixtures of nitrite with secondary and tertiary amines of environmental significance, Food Cosmet. Toxicol. 34:255 (1977).Google Scholar
  4. 4.
    H. Ohshima and H. Bartsch, Quantitative estimation of endogenous nitrosation in humans by monitoring N-nitrosoproline excreted in the urine, Cancer Res. 41:3658 (1981).PubMedGoogle Scholar
  5. 5.
    S. S. Mirvish, Formation of N-nitroso compounds: chemistry, kinetics and in vivo occurrence, Toxicol. Appl. Pharmacol. 31:1325 (1975).CrossRefGoogle Scholar
  6. 6.
    S. S. Mirvish, L. Wallcave, M. Eagen and P. Shubik, Ascorbate-nitrite reaction: Possible means of blocking the formation of carcinogenic N-nitroso compounds, Science 177:65 (1972).PubMedCrossRefGoogle Scholar
  7. 7.
    M. C. Archer, S. R. Tannenbaum, T. Y. Fan and M Weisman, The reactions of nitrite with ascorbate and its relation to nitrosamine formation, J. Natl. Cancer Inst. 154:1203 (1975).Google Scholar
  8. 8.
    W. Fiddler, J. W. Pensabene, E. G. Piotrowski, R. C. Doerr and A. E. Wasserman, Use of sodium ascorbate or erythorbate to inhibit formation of N-nitrosodimethlyamine in frankfurters, J. Food Sci. 38:1084 (1973).CrossRefGoogle Scholar
  9. 9.
    H. Bartsch and R. Montesano, Relevance of nitrosamines to human cancer, Carcinogenesis 5:1381 (1984).PubMedCrossRefGoogle Scholar
  10. 10.
    D. A. Wagner, D. E. G. Shuker, C. Bilmazes, M. Obiedzinski, I. Baker, V. R. Young and S. R. Tannenbaum, Effect of vitamins C and E on endogenous synthesis of N-nitrosoamino acids in humans: precursorproduct studies with 15N-nitrate, Cancer Res. 45:6519 (1985).PubMedGoogle Scholar
  11. 11.
    C. Lintas, J. Fox, S. R. Tannenbaum and P. M. Newberne, In vivo stability of nitrite and nitrosamine formation in the dog stomach. Effect of nitrite and amine concentration and of ascorbic acid, Carcinogenesis 3:161 (1982).PubMedCrossRefGoogle Scholar
  12. 12.
    W. R. Licht, J. G. Fox and W. M. Deen, Effects of ascorbic acid and thiocyanate on nitrosation of proline in the dog stomach, Carcinogenesis 9:373 (1988).PubMedCrossRefGoogle Scholar
  13. 13.
    W. R. Licht, S. R. Tannenbaum and W. M. Deen, Use of ascorbic acid to inhibit nitrosation: Kinetic and Mass transfer considerations for an in vitro system, Carcinogenesis in press.Google Scholar
  14. 14.
    C. D. Leaf, A. J. Vecchio, D. A. Roe and W. M. Hotchkiss, Influence of ascorbic acid dose on N-nitrosoproline formation in humans, Carcinogenesis 8:791 (1987).PubMedCrossRefGoogle Scholar
  15. 15.
    D. A. Wagner, V. R. Young and S. R. Tannenbaum, Mammalian nitrate biosynthesis: incorporation of [15N]-ammonium into nitrate is enhanced by endotoxin treatment, Proc. Natl. Acad. Sci. U.S.A. 80:4518 (1983).PubMedCrossRefGoogle Scholar
  16. 16.
    D. J. Stuehr and M. A. Marietta, Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide, Proc. Natl. Acad. Sci. U.S.A. 82:7738 (1985).PubMedCrossRefGoogle Scholar
  17. 17.
    L. C. Green, D. A. Wagner, K. Ruiz deLuzuriaga, W. Rand, N. Istfan, V. R. Young and S. R. Tannenbaum, Nitrate biosynthesis in man, Proc. Natl. Acad. Sci. U.S.A. 78:7764 (1981).PubMedCrossRefGoogle Scholar
  18. 18.
    D. A. Wagner and S. R. Tannenbaum, Enhancement of nitrate biosynthesis by E. coli lipopolysaccharide, in: “Nitrosamines and Human Cancer”, P. N. Magee, ed., Banbury Report No. 12, Cold Spring Harbor Labs, New York (1982).Google Scholar
  19. 19.
    M. Miwa, D. J. Stuehr, M. A. Marietta, J. S. Wishnok and S. R. Tannenbaum, Nitrosation of amines by stimulated macrophages, Carcinogenesis 8:955 (1987).PubMedCrossRefGoogle Scholar
  20. 20.
    U. Moser, Uptake of ascorbic acid by leukocytes, Ann. N.Y. Acad. Sci. 498:200 (1987).PubMedCrossRefGoogle Scholar
  21. 21.
    J. R. G. Nash, E. Gradwell and D. W. Day, Large-cell intestinal lymphoma occurring in coeliac disease: morphological and immunohistochemical features, Histopathology 10:195 (1986).PubMedCrossRefGoogle Scholar
  22. 22.
    W. E. W. Roediger, M. J. Lawson, S. H. Nance and B. C. Radcliffe, Detectable colonic nitrite levels in inflammatory bowel disease — mucosal or bacterial malfunction?, Digestion 35:199 (1986).PubMedCrossRefGoogle Scholar
  23. 23.
    R. Bockler, H. Meyer and P. Schlag, An experimental study on bacterial colonization, nitrite and nitrosamine production in the operated stomach, J. Cancer Res. Clin. Oncol. 105:62 (1983).PubMedCrossRefGoogle Scholar
  24. 24.
    S. Calmels, H. Ohshima, P. Vincent, A. M. Gounot and H. Bartsch, Screening of microorganisms for nitrosation catalysis at pH 7 and kinetic studies on nitrosamine formation from secondary amines by E. coli strains, Carcinogenesis 6:911 (1985).PubMedCrossRefGoogle Scholar
  25. 25.
    S. Calmels, H. Ohshima, H. Rosenkranz, E. McCoy and H. Bartsch, Biochemical studies on catalysis of nitrosation by bacteria, Carcinogenesis 8:1085 (1987).PubMedCrossRefGoogle Scholar
  26. 26.
    G. DeBernadis, S. Guadagni, M. A. Pistoria, G. Amicucci, C. Masci, C. Herfath, A. Agnifili and M. Carboni, Gastric juice, nitrite and bacteria in gastroduodenal disease and resected stomach, Tumori 96:231 (1983).Google Scholar
  27. 27.
    P. I. Reed, P. L. R. Smith, K. Haines, F. R. House and C. L. Walters, Gastric juice N-nitrosamines in health and gastrointestinal disease, Lancet 11:550 (1981).CrossRefGoogle Scholar
  28. 28.
    D. Ralt and S. R. Tannenbaum, Role of bacteria in nitrosamine formation, N-nitroso compounds, Adv. Chem. 174:159 (1981).Google Scholar
  29. 29.
    S. A. Leach, A. R. Cook, B. C. Challis, M. J. Hill and M. H. Thompson, Bacterially mediated N-nitrosation reactions and endogenous formation of N-nitroso compounds, Proc. of the Ninth International Meeting on N-Nitrosamines, Baden, Austria, September, 1986 (1987).Google Scholar
  30. 30.
    H. Ohshima, S. Calmels, B. Pignatelli, P. Vincent and H. Bartsch, N-Nitrosamine formation in urinary tract infections, Proc. of the Ninth International Meeting on N-nitrosamines, Baden, Austria, September, 1986 (1987).Google Scholar
  31. 31.
    S. R. Tannenbaum, M. C. Archer, J. S. Wishnok and W. W. Bishop, Nitrosamine formation in saliva, J. Natl. Cancer Inst. 60:251 (1978).PubMedGoogle Scholar
  32. 32.
    S. S. Mirvish, J. P. Sams and P. Issenberg, The nitrosating agent in mice exposed to nitrogen dioxide: improved extraction method and localization in the skin, Cancer Res. 43:2550 (1983).PubMedGoogle Scholar
  33. 33.
    H. D. Ross, J. Henion, J. G. Babish and J. H. Hotchkiss, Nitrosating agents from the reaction between methyl oleate and dinitrogen trioxide: Identification and mutagenicity, Food Chemistry 23:207 (1987).CrossRefGoogle Scholar
  34. 34.
    R. Dabora, M. Molina, V. Ng, J. S. Wishnok and S. R. Tannenbaum, in: “N-Nitroso Compounds: Occurrence, Biological Effects and Relevance to Human Cancer”, I. K. O’Neill, R. C. vonBorstel, C. T. Miller, J. Long and H. Bartsch, eds., IARC Scientific Publication No. 57, International Agency for Research on Cancer: Lyon, France (1984).Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Steven R. Tannenbaum
    • 1
  1. 1.Department of Applied Biological SciencesMassachusetts Institute of TechnologyCambridgeUSA

Personalised recommendations