Elimination of Na+-dependent bile acid transporter from small intestine byileum resection increase colonic tumorigenesis in the rat fed deoxycholic acid

Ileal Na+-dependent bile acid transporter (ISBT) constituting a gateway to enterohepatic circulation of bile acids occurs exclusively at the distal si te of the small intestine. In the present study, we examined colonic tumori genesis promoted by deoxycholic acid in relation to the expression of the I SBT. For this purpose, the small intestine of a Fischer-344 rat was resecte d a length of 20 cm above the ileo-cecal valve (ileal resection) or below t he duodenum (jejunal resection). Then, rats were treated with an intraperit oneal injection of azoxymethane (15 mg/kg body wt.) once a week for 3 weeks and fed a 20% casein diet supplemented with 0.2 % deoxycholate for 39 week s. Northern blot analysis demonstrated that the ISBT mRNA was hardly detect able in ileum-resected rats. The excretion of fecal bile acids was 1.5-fold higher in the ileum-resected group than in the jejunum-resected group (P < 0.05), On the contrary, the serum bile acids concentration of ileal-resect ed rats was about one-half of that of jejunum-resected animals (P < 0.05). The tumor incidence and the total tumor number were significantly higher in the ileum-resected group than in the jejunum-resected one (P < 0.05). Inte restingly, no tumor was found at the proximal colon in the jejunum-resected group while tumors developed frequently at the proximal site as well as mi d and distal colon in the ileum-resected group, These observations demonstr ate that malabsorption of bile acids owing to the lack of ISBT enhanced col on tumorigenesis. (C) 1999 Elsevier Science Ireland Ltd. All rights reserve d.