Abstract
Cogent epidemiological and experimental data implicate bile acids as endogenous co-carcinogens in colorectal cancer. A series of experiments was designed to test the ability of sodium deoxycholate (SDC) to promote intestinal hyperplasia and neoplasia in rats (n = 265). The intermediary role of faecal anaerobes was explored in animals receiving oral metronidazole. Intrarectal instillation of SDC trebled tumour yield in functioning large bowel and increased both crypt depth and crypt cell production rate. Metronidazole reduced this tumour promotion without affecting SDC-induced hyperplasia. By contrast, SDC was totally inactive in colon isolated as a Thiry-Vella fistula. Bile acids probably promote colorectal carcinogenesis by stimulating mucosal hyperplasia but only in the presence of faeces.
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- ABRAMS G. D., BAUER H., SPRINZ H. Influence of the normal flora on mucosal morphology and cellular renewal in the ileum. A comparison of germ-free and conventional mice. Lab Invest. 1963 Mar;12:355–364. [PubMed] [Google Scholar]
- Alley P. G., Lee S. P. The increased risk of proximal colonic cancer after cholecystectomy. Dis Colon Rectum. 1983 Aug;26(8):522–524. doi: 10.1007/BF02563745. [DOI] [PubMed] [Google Scholar]
- Aries V., Crowther J. S., Drasar B. S., Hill M. J., Williams R. E. Bacteria and the aetiology of cancer of the large bowel. Gut. 1969 May;10(5):334–335. doi: 10.1136/gut.10.5.334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bradley M. O., Dysart G., Fitzsimmons K., Harbach P., Lewin J., Wolf G. Measurements by filter elution of DNA single- and double-strand breaks in rat hepatocytes: effects of nitrosamines and gamma-irradiation. Cancer Res. 1982 Jul;42(7):2592–2597. [PubMed] [Google Scholar]
- Cohen B. I., Raicht R. F., Deschner E. E., Takahashi M., Sarwal A. N., Fazzini E. Effect of cholic acid feeding on N-methyl-N-nitrosourea-induced colon tumors and cell kinetics in rats. J Natl Cancer Inst. 1980 Mar;64(3):573–578. [PubMed] [Google Scholar]
- Martin M. S., Justrabo E., Jeannin J. F., Leclerc A., Martin F. Effect of dietary chenodeoxycholic acid on intestinal carcinogenesis induced by 1.2 dimethylhydrazine in mice and hamsters. Br J Cancer. 1981 Jun;43(6):884–886. doi: 10.1038/bjc.1981.130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray W. R., Backwood A., Trotter J. M., Calman K. C., MacKay C. Faecal bile acids and clostridia in the aetiology of colorectal cancer. Br J Cancer. 1980 Jun;41(6):923–928. doi: 10.1038/bjc.1980.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pomare E. W., Heaton K. W. The effect of cholecystectomy on bile salt metabolism. Gut. 1973 Oct;14(10):753–762. [PMC free article] [PubMed] [Google Scholar]
- Reddy B. S., Cohen L. A., McCoy G. D., Hill P., Weisburger J. H., Wynder E. L. Nutrition and its relationship to cancer. Adv Cancer Res. 1980;32:237–345. doi: 10.1016/s0065-230x(08)60363-2. [DOI] [PubMed] [Google Scholar]
- Reddy B. S., Watanabe K., Weisburger J. H., Wynder E. L. Promoting effect of bile acids in colon carcinogenesis in germ-free and conventional F344 rats. Cancer Res. 1977 Sep;37(9):3238–3242. [PubMed] [Google Scholar]
- Reddy B. S., Weisburger J. H., Wynder E. L. Effects of high risk and low risk diets for colon carcinogenesis on fecal microflora and steroids in man. J Nutr. 1975 Jul;105(7):878–884. doi: 10.1093/jn/105.7.878. [DOI] [PubMed] [Google Scholar]
- 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. Cancer. 1977 Jun;39(6):2533–2539. doi: 10.1002/1097-0142(197706)39:6<2533::aid-cncr2820390634>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
- Schattenkerk M. E., Li A. K., Jeppsson B. W., Eggink W. F., Jamieson C. G., Ross J. S., Malt R. A. Cholecystectomy has no influence on frequency of chemically induced colonic cancer in mice. Br J Cancer. 1980 Nov;42(5):791–793. doi: 10.1038/bjc.1980.314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Umpleby H. C., Bristol J. B., Rainey J. B., Williamson R. C. Survival of 727 patients with single carcinomas of the large bowel. Dis Colon Rectum. 1984 Dec;27(12):803–810. doi: 10.1007/BF02553944. [DOI] [PubMed] [Google Scholar]
- Watt P. C., Patterson C. C., Kennedy T. L. Late mortality after vagotomy and drainage for duodenal ulcer. Br Med J (Clin Res Ed) 1984 May 5;288(6427):1335–1338. doi: 10.1136/bmj.288.6427.1335. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williamson R. C. Intestinal adaptation: factors that influence morphology. Scand J Gastroenterol Suppl. 1982;74:21–29. [PubMed] [Google Scholar]
- Williamson R. C., Rainey J. B. The relationship between intestinal hyperplasia and carcinogenesis. Scand J Gastroenterol Suppl. 1984;104:57–76. [PubMed] [Google Scholar]
- Wright N. A., Appleton D. R. The metaphase arrest technique. A critical review. Cell Tissue Kinet. 1980 Nov;13(6):643–663. doi: 10.1111/j.1365-2184.1980.tb00503.x. [DOI] [PubMed] [Google Scholar]
- Wynder E. L., Shigematsu T. Environmental factors of cancer of the colon and rectum. Cancer. 1967 Sep;20(9):1520–1561. doi: 10.1002/1097-0142(196709)20:9<1520::aid-cncr2820200920>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]

