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The role of nitrate, nitrite and N-nitrosamines in carcinogenesis of colon tumours following ureterosigmoidostomy

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Summary

Urinary diversion in both a rat model for ureterosigmoidostomy and in ureterosigmoidostomy patients result in an increased incidence of colon tumours. Bacterial and chemical investigations on feces-urine mixtures from both the rat model and ureterosigmoidostomy patients showed the presence of a complex nitrate-reducing bacterial flora in both rats and humans. This bacterial flora actively reduced urinary nitrate to nitrite in humans and increased the endogenous formation of N-nitroso compounds. No evidence of urinary nitrate reduction and increased nitrosamine formation in the rectosigmoid of rats was found. The results support the N-nitrosamine theory of carcinogenesis of the colon following ureterosigmoidostomy in humans, but not in rats. As the rat model induces colon carcinomas, factors other than the increased endogenous formation of N-nitroso compounds in the rectosigmoid may contribute to the initiation of colon carcinomas following ureterosigmoidostomy.

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References

  1. Archer MC, Saul RL, Lee LJ, Bruce WR (1981) Analysis of nitrate, nitrite and nitrosamines in human feces. In: Bruce WR, Correa P, Lipkin M, Tannenbaum SR, Wilkins TD (eds) Banbury report 7—Gasterointestinal cancer: endogenous factors. Cold Spring Harbor Laboratory, New York, p 321

    Google Scholar 

  2. Bartholomew B, Hill MJ (1984) Th pharmacology of dietary nitrate and the origin of urinary nitrate. Food Chem Toxicol 22:789

    Google Scholar 

  3. Calmels S, Ohshima H, Rosenkranz H, McCoy E, Bartsch H (1987) Biochemical studies on the catalysis of nitrosation by bacteria. Carcinogenesis 8:1085

    Google Scholar 

  4. Cohen MS, Hilz ME, Davis CP, Anderson MD (1987) Urinary carcinogen (nitrosamine) production in a rat animal model for ureterosigmoidostomy. J Urol 138:449

    Google Scholar 

  5. Crissey MM, Steele GD, Gittes RF (1980) Rat model for carcinogenesis in ureterosigmoidostomy. Science 207:1079

    Google Scholar 

  6. Daher N, Gautier R, Abourachid H, Decaens C, Bara J (1988) Rat colonic carcinogenesis after ureterosigmoidostomy: pathogenesis and immunohistological study. J Urol 139:1331

    Google Scholar 

  7. Dailey RE, Braunberg RC, Blaschka AM (1975) The absorption, distribution, and excretion of (14C) nitrosoproline by rats. Toxicology 3:23

    Google Scholar 

  8. Davis CP, Cohen MS, Anderson MD, Gruber MB, Warren MM (1985) Urothelial hyperplasia and neoplasia. II. Detection of nitrosamines and interferon in chronic urinary tract infections in rats. J Urol 134:1002

    Google Scholar 

  9. Druckrey H, Preussmann R, Ivankovic S, Schmähl D (1967) Carcinogenesis and organotropic action of 65 different N-nitroso compounds in BD rats (in German). Z Krebsforsch 69:103

    Google Scholar 

  10. Dull BJ, Hotchkiss JH (1984) Activated oxygen and mammalian nitrate biosynthesis. Carcinogenesis 5:1161

    Google Scholar 

  11. Dull BJ, Gittes RF, Goldman P (1988) Nitrate production and phagocyte activation: differences among Sprague-Dawley, Wistar-Furth and Lewis rats. Carcinogenesis 9:625

    Google Scholar 

  12. Eisenbrand G, Spiegelhalder B, Preussmann R, (1981) Analysis of human biological samples for nitrosamine content. In: Bruce WR, Correa P, Lipkin M, Tannenbaum SR, Wilkins TD (eds) Banbury report 7—Gastrointestinal cancer: endogenous factors. Cold Spring Harbor Laboratory, New York, p 275

    Google Scholar 

  13. Eraklis JA, Folkman MJ (1978) Adenocarcinoma at the site of ureterosigmoidostomies for exstrophy of the bladder. J Pediatr Surg 13:730

    Google Scholar 

  14. Gittes RF (1986) Carcinogenesis in ureterosigmoidostomy. Urol Clin North Am 13:201

    Google Scholar 

  15. Gomez RF, Tannenbaum SR, Savoca J, Ralt D, Rockowitz N (1980) Heterotrophic nitrification by intestinal microorganisms. Cancer 45:1066

    Google Scholar 

  16. Gracey M, Kay R, Bishop RF, Smith ED, Anderson CHM (1971) Mucosal morphology and bacterial flora of ilealconduits. Invest Urol 8:596

    Google Scholar 

  17. Green LC, Tannenbaum SR, Goldman P (1981) Nitrate synthesis in the germfree and conventional rat. Science 212:56

    Google Scholar 

  18. Hammer E (1929) Cancer of the sigmoid colon ten years after ureter implanation and bladder exstrophy (in French). J Urol 28:260

    Google Scholar 

  19. Hibbs JB Jr., Taintor RR, Vavrin Z (1987) Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science 235:474

    Google Scholar 

  20. Iyengar R, Stuehr DJ, Marletta MA (1987) Macrophagesynthesis of nitrite, nitrate, and N-nitrosamines: precursors and role of the respiratory burst. Proc Natl Acad Sci USA 84:6369

    Google Scholar 

  21. Kälble T, Möhring K, Tricker AR, Ovelgönne H-R, Schlag P (1989) Adenocarcinoma of the colon following ureterosigmoidostomy (in German). Aktuel Urol 20:173

    Google Scholar 

  22. Klubes P, Cerna I, Rabinowitz AD, Jondorf WR (1972) Factors affecting dimethylnitrosamine formation from simple precursors by rat intestinal bacteria. Food Chem Toxicol 10:757

    Google Scholar 

  23. Lee L, Archer MC, Bruce WR (1981) Absence of volatile nitrosamines in human feces. Cancer Res 41:3992

    Google Scholar 

  24. Mallet AK, Rowland IR, Walters DG, Gangolli SD, Cottrell RC, Massey RC (1985) The role of oral nitrate in the nitrosation of (14C)proline by conventional micro-flora and germ-free rats. Carcinogenesis 6:1585

    Google Scholar 

  25. Massey RC, Key PE, Mallett AK, Rowland IR (1988) An investigation of the endogenous formation of apparent total N-nitroso compounds in conventional microflora and germ-free rats. Food Chem Toxicol 26:595

    Google Scholar 

  26. Miwa M, Stuehr DJ, Marletta MA, Wishnok JS, Tannenbaum SR (1987) Nitrosation of amines by stimulated macrophages. Carcinogenesis 8:955

    Google Scholar 

  27. Moorcraft J, DuBoulay CEH, Isaacson P, Atwell JD (1983) Changes in the mucosa of colon conduits with particular reference of the risk of malignant change. Br J Urol 55:185

    Google Scholar 

  28. Ohshima H, Bereziat J-C, Bartsch H (1982) Monitoring N-nitrosamino acids excreted in the urine and feces of rats as an index for endogenous nitrosation. Carcinogenesis 3:115

    Google Scholar 

  29. Parsons ChD, Thomas MH, Garrett RA (1977) Colonic adenocarcinoma: a delayed complication of ureterosigmoidostomy. J Urol 118:31

    Google Scholar 

  30. Preussmann R, Stewart BW (1984) N-Nitroso carcinogens. In: Searle CE (ed) Chemical carcinogens. ACS Monograph 182, American Chemical Society, Washington, DC, p 643

    Google Scholar 

  31. Radomski JL, Greenwald D, Hearn WL, Block NL, Woods FM (1978) Nitrosamine formation in bladder infections and its role in the etiology of bladder cancer. J Urol 120:48

    Google Scholar 

  32. Saul RL, Kabir SH, Cohen Z, Bruce WR, Archer MC (1981) Reevaluation of nitrate and nitrite levels in the human intestine. Cancer Res 41:2280

    Google Scholar 

  33. Saul RL, Archer MC (1984) Oxidation of ammonia and hydroxylamine to nitrate in the rat and in vitro. Carcinogenesis 5:77

    Google Scholar 

  34. Schultz DS, Deen WM, Karel SF, Wagner DA, Tannenbaum SR (1985) Pharmacokinetics of nitrate in humans: role of gastrointestinal absorption and metabolism. Carcinogenesis 6:847

    Google Scholar 

  35. Starting JR, Uehling DT, Gilchrist KW, (1984) Value of colonoscopy after ureterosigmoidostomy. Surgery 96:784

    Google Scholar 

  36. Stewart M, Hill MJ, Pugh RCB, Williams JP (1981) The role of N-nitrosamine in carcinogenesis at the ureterocolic anastomosis. Br J Urol 53:115

    Google Scholar 

  37. Stewart M, Macrae FA, Williams CB (1982) Neoplasia and ureterosigmoidostomy: A colonoscopy survey. Br J Surg 69:414

    Google Scholar 

  38. Stewart M (1986) Urinary diversion and bowel cancer. Ann Coll Surg Engl 68:98

    Google Scholar 

  39. Silverman SH, Woodhouse CRJ, Strachan JR, Cumming J, Keighley MRB (1986) Long-term management of patients who have had urinary diversions into colon. Br J Urol 58:634

    Google Scholar 

  40. Stribling MD, Cohen MS, Davis CP, Anderson MD, Warren MM (1988) Decrease in carcinogen (nitrosamine) levels in an animal model for ureterosigmoidostomy with administration of ascorbic acid. South Med J 81:S96

  41. Stuehr DJ, Marletta MA (1987) Synthesis of nitrite and nitrate in murine macrophage cell lines. Cancer Res 47:5590

    Google Scholar 

  42. Tricker AR, Preussmann R (1987) Influence of Cysteine and nitrate on the endogenous formation of N-nitrosamino acids. Cancer Lett 34:39

    Google Scholar 

  43. Tricker AR, Preussmann R (1988) The occurrence of N-nitroso compounds in zarda tobacco. Cancer Lett 42:113

    Google Scholar 

  44. Tricker AR, Mostafa MH, Spiegelhalder B, Preussmann R (1989) Urinary excretion of nitrate, nitrite and N-nitrosocompounds in schistosomiasis and bilharzia bladder cancer patients. Carcinogenesis 10:547

    Google Scholar 

  45. Urdaneta LF, Duffell D, Creevy CD, Aust JB (1966) Late development of primary carcinoma of the colon following ureterosigmoidostomy. Ann Surg 164:503

    Google Scholar 

  46. Wagner DA, Shuker DEG, Bilmazes Ch, Obiedzinski M, Baker I, Young VR, Tannenbaum SR (1985) Effect of vitamins C and E on endogenous synthesis of N-nitrosamino acids in humans: precursor-product studies with (15N) nitrate. Cancer Res 45:6519

    Google Scholar 

  47. Wang T, Kakizoe T, Dion P, Furrer R, Varghese AJ, Bruce WR (1978) Volatile nitrosamines in normal human faeces. Nature 276:280

    Google Scholar 

  48. Ward FW, Coates ME (1986) Nitrate reduction, gastro-intestinal pH and N-nitrosation in genotobiotic and conventional rats. Food Chem Toxicol 24:17

    Google Scholar 

  49. Witter JP, Balish E (1979) Distribution and metabolism of ingested nitrate and nitrite ions in germfree and conventional-flora rats. Appl Environ Microbiol 38:861

    Google Scholar 

  50. Witter JP, Gatley SJ, Balish E (1979) Distribution of nitrogen-13 from labeled nitrate (13NO3) in human and rats. Science 204:411

    Google Scholar 

  51. Witter JP, Gatley SJ, Balish E (1981) Evaluation of nitrate synthesis by intestinal microorganisms in vivo. Science 213:449

    Google Scholar 

  52. Witter JP, Balish E, Gatley SJ (1982) Origin of excess urinary nitrate in the rat. Cancer Res 42:3654

    Google Scholar 

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Authors and Affiliations

  1. Urological Department, University of Heidelberg, Heidelberg, FRG

    T. Kälble, K. Möhring & G. Staehler

  2. Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg, FRG

    A. R. Tricker & M. R. Berger

  3. Institute of Hygienics, University of Heidelberg, Heidelberg, FRG

    H. Geiss

Authors
  1. T. Kälble
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  2. A. R. Tricker
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  3. K. Möhring
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  4. M. R. Berger
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  5. H. Geiss
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  6. G. Staehler
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Kälble, T., Tricker, A.R., Möhring, K. et al. The role of nitrate, nitrite and N-nitrosamines in carcinogenesis of colon tumours following ureterosigmoidostomy. Urol. Res. 18, 123–129 (1990). https://doi.org/10.1007/BF00302472

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  • DOI: https://doi.org/10.1007/BF00302472

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