Summary
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.
Similar content being viewed by others
Abbreviations
- MNNG:
-
N-methyl-N′-nitro-N-nitrosoguanidine
References
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
Caygill C, Hill M, Kirkham J, Northfield T (1986) Mortality from gastric cancer following gastric surgery for peptic ulcer. Lancet I:929–931
Cohen A, Geller SA, Horowitz I, Toth LS, Werther JL (1984) Experimental models for gastric leiomyosarcoma. Cancer 53:1088–1092
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
Domellöf L (1979) Gastric carcinoma promoted by alkaline reflux gastritis. Med Hypotheses 5:463–476
Domelöff L, Janunger KG (1977) The risk for gastric carcinoma after partial gastrectomy. Am J Surg 134:581–584
Domelöff L, Reddy BS, Weihburger JH (1980) Microflora deconjugation of bile acids in alkaline reflux after partial gastrectomy. Am J Surg 140:290–295
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
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
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
Helsingen N, Hillested L (1956) Cancer development in the gastric stump after partial gastrectomy for ulcer. Ann Surg 143:173–179
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
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
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
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
Liavaag K (1962) Cancer development in gastric stump after partial gastrectomy for peptic ulcer. Ann Surg 155:103–106
Morgenstern L, Yamakawa T, Seltzer D (1973) Carcinoma of the gastric stump. Am J Surg 125:29–38
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
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
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
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
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
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
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
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
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
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
Silverman SJ, Andrews AW (1977) Bile acids. Co-mutagenic activity in the Salmonella-mammalian microsome mutagenicity test. J Natl Cancer Inst 59:1557–1559
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
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
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kuwahara, A., Saito, T. & Kobayashi, M. Bile acids promote carcinogenesis in the remnant stomach of rats. J Cancer Res Clin Oncol 115, 423–428 (1989). https://doi.org/10.1007/BF00393330
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00393330