Skip to main content
Journal of Cancer Research and Clinical Oncology logoLink to Journal of Cancer Research and Clinical Oncology
. 1989 Sep;115(5):423–428. doi: 10.1007/BF00393330

Bile acids promote carcinogenesis in the remnant stomach of rats

A Kuwahara 1,, T Saito 1, M Kobayashi 1
PMCID: PMC12211570  PMID: 2808479

Abstract

We examined the tumor-promoting activity of sodium taurocholate in the remnant stomach of rats. Ninety male Wistar rats, 8 weeks of age, were separated into four groups. In group I, the rats were given N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) at a concentration of 83 mg/l in drinking water for 15 weeks, and distal partial gastrectomy was performed by Roux-en-Y procedure to prevent duodenal reflux into the remnant stomach. Thereafter, a diet containing 0.25% sodium taurocholate was given for 43 weeks. The group II rats were given MNNG and gastrectomy and were then given the usual commercial diet. The rats in group III were given gastrectomy and sodium taurocholate and no previous administration of MNNG. Only MNNG was given to the rats in group IV. The incidence of malignant tumors in the remnant stomach was 40.9% (9/22), 27.3% (6/22), and 0% (0/22) in groups I, II, and III, respectively, while the incidence in the area corresponding to the remnant stomach (control) was 8.3% (2/24) in group IV. The difference in tumor incidence was statistically significant (P<0.05) between groups I and IV but not between groups II and IV, and not between groups I and II. Six of nine tumors in group I and all six tumors in group II were located in the anastomotic area. These results suggest that sodium taurocholate promotes tumor production in the remnant stomach, and that the surgical procedure may well be associated with this enhanced tumor occurrence.

Key words: Bile acid, Surgical procedure, Rat remnant stomach, Carcinogenesis

Abbreviation

MNNG

N-methyl-N′-nitro-N-nitrosoguanidine

References

  1. Bandaru SR, Watanabe K, Weisburger JH, Wynder EL (1977) Promoting effect of bile acids in colon carcinogenesis germ-free and conventional F244 rats. Cancer Res 37:3238–3242 [PubMed] [Google Scholar]
  2. Caygill C, Hill M, Kirkham J, Northfield T (1986) Mortality from gastric cancer following gastric surgery for peptic ulcer. Lancet I:929–931 [DOI] [PubMed] [Google Scholar]
  3. Cohen A, Geller SA, Horowitz I, Toth LS, Werther JL (1984) Experimental models for gastric leiomyosarcoma. Cancer 53:1088–1092 [DOI] [PubMed] [Google Scholar]
  4. Dahm K, Werner B, Eichen R (1979) Experimental cancer of the gastric stump. In: Herfart CH, Schlag P (eds) Gastric cancer. Springer, Berlin Heidelberg New York, pp 44–59 [Google Scholar]
  5. Domellöf L (1979) Gastric carcinoma promoted by alkaline reflux gastritis. Med Hypotheses 5:463–476 [DOI] [PubMed] [Google Scholar]
  6. Domelöff L, Janunger KG (1977) The risk for gastric carcinoma after partial gastrectomy. Am J Surg 134:581–584 [DOI] [PubMed] [Google Scholar]
  7. Domelöff L, Reddy BS, Weihburger JH (1980) Microflora deconjugation of bile acids in alkaline reflux after partial gastrectomy. Am J Surg 140:290–295 [DOI] [PubMed] [Google Scholar]
  8. Fujiki H, Mori M, Nakayasu M, Terada M, Sugimura T (1979) A possible naturally occurring tumor promoter, teleocidin B, from Streptomyces. Biochem Biophys Res Commun 90:996–983 [DOI] [PubMed] [Google Scholar]
  9. Furihata C, Sato Y, Hosaka M, Matsushima T, Furukawa F, Takahashi M (1984) NaCl induced ornithine decarboxylase and DNA synthesis in rat stomach mucosa. Biochem Biophys Res Commun 121:1027–1032 [DOI] [PubMed] [Google Scholar]
  10. Furihata C, Takezawa R, Matsushima T, Tatematsu M (1987) Potential tumor-promoting activity of bile acids in rat glandular stomach. Jpn J Cancer Res (Gann) 78:32–39 [PubMed] [Google Scholar]
  11. Helsingen N, Hillested L (1956) Cancer development in the gastric stump after partial gastrectomy for ulcer. Ann Surg 143:173–179 [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kaibara N, Yurugi S, Koga S (1984) Promoting effect of bile acids on the chemical transformation of C3H/10T1/2 fibroblasts in vitro. Cancer Res 44:5482–5485 [PubMed] [Google Scholar]
  13. Kobori O, Watanabe J, Shimizu M, Shoji M, Morioka Y (1984) Enhancing effect of sodium taurocholate on N-methyl-N′-nitro-N-nitrosoguanidine induced stomach tumorigenesis in rats. Jpn J Cancer Res (Gann) 75:651–654 [PubMed] [Google Scholar]
  14. Kondo K, Suzuki H, Nagayo T (1984) The influence of gastric jejunal anastomosis on gastric carcinogenesis in rats. Jpn J Cancer Res (Gann) 75:362–396 [PubMed] [Google Scholar]
  15. Lee S, Iida M, Yao T, Shindo S, Fujishima M, Okabe H (1988) Long-term follow-up of 2529 patients with gastric and duodenal ulcer: survival rate and causes of death. Gastroenterology 94:381–386 [DOI] [PubMed] [Google Scholar]
  16. Liavaag K (1962) Cancer development in gastric stump after partial gastrectomy for peptic ulcer. Ann Surg 155:103–106 [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Morgenstern L, Yamakawa T, Seltzer D (1973) Carcinoma of the gastric stump. Am J Surg 125:29–38 [DOI] [PubMed] [Google Scholar]
  18. Narisawa T, Nagadia NE, Weisburger JH, Wynder EL (1974) Promoting effect of bile acids on colon carcinogenesis after intrarectal instillation of N-methyl-N′-nitro-N-nitrosoguanidine in rats. J Natl Cancer Inst 53:1093–1097 [DOI] [PubMed] [Google Scholar]
  19. Nishidoi H, Koga S, Kaibara N (1984) Possible role of duodenogastric reflux on the development of remnant gastric carcinoma induced by N-methyl-N′-nitro-N-nitrosoguanidine in rats. JNCI 72:1431–1435 [PubMed] [Google Scholar]
  20. Noda K, Umeda M, Ono T (1981) Effect of various chemicals including bile acids and chemical carcinogens on the inhibition of metabolic cooperation. Jpn J Cancer res (Gann) 72:772–776 [PubMed] [Google Scholar]
  21. O'Brien TG, Simsiman RC, Boutwell RK (1975) Induction of the polyamine-biosynthetic enzymes in mouse epidermis by tumor-promoting agents. Cancer Res 35:1662–1670 [PubMed] [Google Scholar]
  22. Saito T, Inokuchi K, Takayama S, Sugimura T (1970) Sequential morphological changes in N-methyl-N′-nitro-N-nitrosoguanidine carcinogenesis in the glandular stomach of rats. J Natl Cancer Inst 44:769–783 [PubMed] [Google Scholar]
  23. Saito T, Kuwahara A, Kobayashi M (1986) Induction of ornithine decarboxylase activity in rat glandular stomach mucosa by bile acids. Jpn J Cancer Res (Gann) 77:739–742 [PubMed] [Google Scholar]
  24. Salmon RJ, Laurent M, Thierry JP (1984) Effect of taurocholic acid feeding on N-methyl-N′-nitrosoguanidine (MNNG) induced gastric tumors. Cancer Lett 22:315–320 [DOI] [PubMed] [Google Scholar]
  25. Salmon RJ, Merle S, Zafrani B, Decosse JJ, Sherlock P, Deschner EE (1985) Gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine role of gastrectomy and duodenal reflux. Jpn J Cancer Res (Gann) 76:167–172 [PubMed] [Google Scholar]
  26. Sandler RS, Johnson MD, Holland KL (1984) Risk of stomach cancer after gastric surgery for benign condition: a case control study. Dig Dis Sci 29:703–708 [DOI] [PubMed] [Google Scholar]
  27. Sano C, Kumashiro R, Saito T, Inokuchi K (1984) Promoting effect of partial gastrectomy on carcinogenesis in the remnant stomach of rats after oral administration of N-methyl-N′-nitro-N-nitrosoguanidine. Oncology 41:124–128 [DOI] [PubMed] [Google Scholar]
  28. Silverman SJ, Andrews AW (1977) Bile acids. Co-mutagenic activity in the Salmonella-mammalian microsome mutagenicity test. J Natl Cancer Inst 59:1557–1559 [DOI] [PubMed] [Google Scholar]
  29. Takano S, Matsushima M, Erturk E, Bryan GT (1981) Early induction of rat colonic epithelial ornithine and S-adenosyl-l-methionine decarboxylase activities by N-methyl-N′-nitro-N-nitrosoguanidine or bile salts. Cancer Res 41:624–628 [PubMed] [Google Scholar]
  30. Viste A, Bjornestad E, Opheim P, Skarstein A, Thunold J, Hartveit F, Eide GE, Eide TJ, Soreide O (1986) Risk of carcinoma following gastric operation for benign disease. Lancet II:502–504 [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cancer Research and Clinical Oncology are provided here courtesy of Springer

RESOURCES