Medical Hypotheses
Volume 59, Issue 4 , Pages 398-405 , October 2002

Three hypotheses linking bile to carcinogenesis in the gastrointestinal tract: certain bile salts have properties that may be used to complement chemotherapy

  • Dennis H Stamp

      Affiliations

    • Corresponding Author InformationCorrespondence to: Dennis H. Stamp, 23 Fairmar Avenue, Toronto, Ont., Canada M8Y 2C7

Received 3 January 2001 ,Accepted 31 October 2001.

References 

  1. Fein M, Peters JH, Chandrasoma P, Ireland AP, et al.  Duodenoesophageal reflux induces esophageal adenocarcinoma without exogenous carcinogen. J. Gastroint. Surgery. 1998;2(3):260–268
  2. Batzri S, Harmon J, Schweitzer EJ, Toles R. Bile acid accumulation in the gastric mucosal cells. Soc. Exp. Biol. Med. 1991;197:393–399
  3. Schweitzer EJ, Bass BL, Batzri S, Harmon JW. Bile acid accumulation by rabbit esophageal mucosa. Dis. Sci. 1986;31:1105–1113
  4. Ouatu-Lascar R, Fitzgerald RC, Triadafilopoulos G. Differentiation and proliferation in Barrett's esophagus and the effects of acid suppression. Gastroenterology. 1999;117:327–335
  5. Ireland AP, Peters JH, Smyrk TC, et al.  Gastric juice protects against the development of esophageal-adenocarcinoma in the rat. Ann. Surg. 1996;224(3):358–371
  6. Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. The New Eng. J. Med. 1999;340(11):825–831
  7. Goldstein SR, Yang G, Curtis SK, et al.  Development of esophageal metaplasia and adenocarcinoma in a rat surgical model without the use of a carcinogen. Carcinogenesis. 1997;18(11):2265–2270
  8. Gillen P, Keeling P, Byrne , et al.  Implications of duodenogastric reflux in the pathogenesis of Barrett's esophagus. Br. J. Surg. 1988;75:540–543
  9. Kauer WK, Peters JH, DeMeester TR, et al.  Composition and concentration of bile acid reflux into the esophagus of patients with gastroesophageal reflux diseases. Surgery. 1997;122(5):874–881
  10. Gotley DC, Morgan AP, Cooper MJ. Bile acid concentration in the refluxate of patients with reflux esophagitis. Br. J. Surg. 1988;75:587–590

  11. Bile concentrate; known as `Sodium choleate', is a commercial preparation of cow's/pig's bile supplied by Sigma Chemicals; St. Louis, USA. It consists of the sodium salts of free and conjugated bile acids all in the same ratio as exist in vivo

  12. Salmon RJ, Laurent M, Thierry JP. Effects of taurocholic acid feeding on MNNG induced gastric tumors. Cancer Lett. 1984;22:315–320
  13. Simanowski UA, Seltz HK, Czygan P, et al.  Chronic ursodeoxycholic acid- and chenodeoxycholic acid-feeding-induced changes of colon mucosal cell proliferation in rats. JNCI. 1987;79(1):163–166
  14. Oichiro K, Toshio S, Mamoru M, et al.  Enhancing effect of bile and bile acids on stomach tumorigenesis induced by MNNG in Wistar rats. JNCI. 1984;73(4):853–861
  15. Blaser M, cited by Christensen D, The rise and fall of bacterium H. pylori. Science News 1999; 156: 234–236
  16. Scott DR, Weeks D, Hong C, et al.  The role of internal urease in acid resistence of H. Pylori. Gastroenterology. 1998;114:58–70
  17. Hill MJ. Bile flow and colon cancer. Mutat Res. 1990;238:3130–3320
  18. Hoffmann AF. The entero-hepatic circulation of bile acids in man. Adv. Int. Med. 1976;21:501
  19. Coombs MM, Bhatt TS, Croft CJ. Correlation between carcinogenicity and chemical structure in cyclopenta [a] phenantrenes. Cancer Res. 1973;33:832–837
  20. Goldin B, Sherwood L, Gorbach MD. Effect of antibiotics on incidence of rat intestinal tumor induced by DMH. JNCI. 1981;67(4):877–880
  21. Reddy BS, Watanabe K, Weisburger J, Wynder E. Promoting effect of bile acids in colon carcinogenesis in germ free and conventional F344 rats. Cancer Res. 1977;37:3238–3242
  22. Rainey JB, Maeda M, Williams C, Williamson RCN. The carcinogenic effect of intra- rectal deoxycholate in rats is reduced by oral metronidazole. Br. J. Cancer. 1984;49:631–636
  23. Sontag S, Schnell T, Chejfec G, et al.  Barrett's esophagus and colonic tumors. The Lancet. 1985;946–949
  24. Robertson DA, Ayers RC, Smith CL. Screening for colonic cancer in patients with Barrett's esophagus. Br. Medical J. 1989;298:650
  25. Nair PP, Kritchevski D. The Bile Acids: Chem, Physiol and Metabolism Vol 1: Chemistry. New York, London: Plenum Press; 1971;
  26. Roda A, Hofmann AF, Mysels K editors, The influence of bile salts, structure on self-association, in aqueous solutions. J Biol Chem 1983; 258(10): 6362–6383
  27. Garewal H, Burnstein H, Burastein C, et al.  Reduced bile acid-induced Apoptosis in `normal' colorectal mucosa: a potential marker for cancer risk. Cancer Res. 1996;56:1480
  28. Bernstein C, Bernstein H, Garewal , et al.  A bile acid-induced apoptosis assay for colon risk and associated quality control studies. Cancer Res. 1999;59:2353
  29. Schlottmann K, Wachs FP, Krieg RC, et al.  Characterization of Bile salt-induced apoptosis colon cancer cell lines. Cancer Res. 2000;60:4270
  30. Nishioka NS, Mycek M. Initial experience with a real-time video processor for enhancing endoscopic image contrast. Gastrointest. Endoscopy. 1998;48(1):62

☆ Abbreviations used: BE, Barrett's Esophagus; GERD, gastro esophageal reflux disease; GDEA, gastro duodeno esophageal anastomosis; GC, glycocholic acid; EAC, esophageal adenocarcinoma; MNNG, Methyl-N-nitro-N-nitrosoguanidine; PAH, Polycyclic Aromatic Hydrocarbons; “Bile salts” and “bile acids” are used interchangeably.

PII: S0306-9877(02)00125-1

Medical Hypotheses
Volume 59, Issue 4 , Pages 398-405 , October 2002

Article Tools