Summary
Wistar rats spontaneously develop adenomatous polyps with cell dysplasia (Figs. 2 and 3) and finally, adenocarcinomas (Fig. 1) at the preternatural anus 120–200 days after the formation of a double loop colostomy. With respect to the potential significance of bile acid metabolites in the pathogenesis of colonic cancer, the effect of continuous oral administration of chenodeoxycholic acid (CDCA) on the rate of carcinomas at the preternatural anus was examined. This animal model gained special interest because until now the possible cocarcinogenic rule of bile metabolites was generally demonstrated only after additional administration of chemical carcinogens like dimethylhydracin or nitrosoguanidin. Of ten rats in the CDCA-treated group, three already showed a malignant transformation to adenocarcinomas at the preternatural anus 60 days after a colostomy (Fig. 4). Apparently the alteration of natural ecologic conditions diminishes the resistance against external and internal carcinogenic or cocarcinogenic agents. The rule of bile acid metabolites is discussed under these circumstances.
Zusammenfassung
120–200 Tage nach Anlage einer doppelläufigen Colostomie entwickeln Wistar-Ratten im Bereich des Anus praeter spontan Adenocarcinome. Im Hinblick auf die mögliche Bedeutung von Gallensäuremetaboliten für die Pathogenese des Coloncarcinoms wurde an colostomierte Ratten Chenodesoxycholsäure verfüttert. Bereits 60 Tage nach Colostomie fand sich bei 3 von 10 Ratten eine maligne Transformation der Dickdarmschleimhaut im Bereich des Kunstafters. Die an diesem neuartigen Tiermodell gewonnene Beobachtung läßt eine cocarcinogene Aktivität der Gallensäuren bzw. ihrer bakteriellen Metaboliten vermuten.
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Literatur
Aries, V., Crowther, J. B., Drasar, B. S., Hill, M. J., Williams, R. E. O.: Bacteria and the aetiology of cancer of the large bowel. Gut10, 334–335 (1969)
Berg, J. W., Howell, M. A.: The geographic pathology of bowel cancer. Cancer [Suppl.]34, 807–814 (1974)
Cook, J. W., Kennaway, E. L., Kennaway, N. M.: Production of tumors in mice by deoxycholic acid. Nature145, 627–629 (1940)
Dahm, K., Eichen, R., Mitschke, H.: Das Krebsrisiko im Resektionsmagen. Langenbecks Arch. Chir.344, 71–82 (1977)
Haenszel, W., Berg, J. W., Segi, M., Kurihara, M., Locke, F. B.: Large bowel cancer in Hawaiien Japanese. J. Natt. Cancer Inst.51, 1765–1779 (1973)
Hill, M. J.: Bacteria and the etiology of colonic cancer. Cancer34, 815–818 (1974)
Hill, M. J.: The role of colon anaerobes in the metabolism of bile acids and steroids, and its relation to colon cancer. Cancer36, 2387–2400 (1975)
Höpker, W.-W., Bohrer, M. H., Storch, B.: Epidemiologische Untersuchungen zur Pathogenese des Dickdarmkarzinoms. Z. Gastroenterol.17, 162–170 (1979)
Leuschner, U., Schneider, M., Loos, R., Kurtz, W.: Morphologische Untersuchungen zur Toxizität oral verabreichter Chenodesoxycholsäure an Leber, Magen-Darmtrakt, Niere und Nebenniere der Ratte. Res. Exp. Med.171, 41–55 (1977)
Narisawa, T., Magadia, N. E., Weisburger, J. H., Wynder, E. L.: 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 (1974)
Nigro, N. D., Bhadrachari, N., Campbell, R. L.: A rat model for studying colon cancer. Effect of cholestyramine on induced tumors. Dis. Colon Rectum16, 438–443 (1973)
Reddy, B. S., Weisburger, J. H., Wynder, E. L.: Effect of high risk and low risk diets for colon carcinogenesis on fecal microflora and steroids in men. J. Nutr.105, 878–884 (1975)
Reddy, B. S.: Role of bile metabolites in colon carcinogenesis. Cancer36, 2401–2406 (1975)
Reddy, B. S., Martin, C. W., Wynder, E. L.: Fecal bile acids and cholesterol metabolites of patients with ulcerative colitis, a high-risk-group for development of colon cancer. Cancer Res.37, 1697–1701 (1977)
Reddy, B. S., Watanabe, K., Weisburger, J. H., Wynder, E. L.: Promoting effect of bile acids in colon carcinogenesis in germ-free and conventional F 344 rats. Cancer Res.37, 3238–3242 (1977)
Reddy, B. S., Wynder, E. L.: Metabolic epidemiology of colon cancer. Fecal bile acids and neutral sterols in colon cancer patients and patients with adenomatous polyps. Cancer39, 2533–2539 (1977)
Sauer, H.-D., de Heer, K., Mitschke, H.: Orale Chenodesoxycholsäuretherapie und kolorektales Karzinom — eine experimentelle Studie. Z. Gastroenterol.17, 236–243 (1979)
Werner, B., de Heer, K., Mitschke, H.: Cholecystectomy and carcinoma of the colon. Z. Krebsforsch.88, 223–230 (1977)
Winkler, R., Heitmann, C., Otto, H. F.: Das Carcinom am Anus praeter. Langenbecks Arch. Chir.343, 229–241 (1977)
Winkler, R.: Das kolorektale Karzinom. Untersuchungen zur Epidemiologie und tierexperimentellen Karzinogenese. Fortschr. Med.96, 115–119 (1978)
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Sauer, H.D., Winkler, R., Thoma, G. et al. Carcinompromotion am Anus praeter durch Gallensäuren. Langenbecks Arch Chiv 350, 255–262 (1980). https://doi.org/10.1007/BF01237636
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DOI: https://doi.org/10.1007/BF01237636