Reference SummaryMahmoud NN, Carcinogenesis 1999 Feb;20(2):299-303

Title

 Administration of an unconjugated bile acid increases duodenal tumors in a murine model of familial adenomatous polyposis.

Authors

 Mahmoud NN; Dannenberg AJ; Bilinski RT; Mestre JR; Chadburn A; Churchill M; Martucci C; Bertagnolli MM

Journal

 Carcinogenesis

Volume

 20

Issue

 2

Year

 1999

Pages

 299-303

Abstract

 Intestinal carcinogenesis involves the successive accumulation of multiple genetic defects until cellular transformation to an invasive phenotype occurs. This process is modulated by many epigenetic factors. Unconjugated bile acids are tumor promoters whose presence in intestinal tissues is regulated by dietary factors. We studied the role of the unconjugated bile acid, chenodeoxycholate, in an animal model of familial adenomatous polyposis. Mice susceptible to intestinal tumors as a result of a germline mutation in Apc (Min/+ mice) were given a 10 week dietary treatment with 0.5% chenodeoxycholate. Following this, the mice were examined to determine tumor number, enterocyte proliferation, apoptosis and beta-catenin expression. Intestinal tissue prostaglandin E2 (PGE2) levels were also assessed. Administration of chenodeoxycholate in the diet increased duodenal tumor number in Min/+ mice. Promotion of duodenal tumor formation was accompanied by increased beta-catenin expression in duodenal cells, as well as increased PGE2 in duodenal tissue. These data suggest that unconjugated bile acids contribute to periampullary tumor formation in the setting of an Apc mutation.

Links

 J:53701 – MGI References
10069468 – National Library of Medicine/PubMed

Strain Notes

Strain Note
C57BL/6J-ApcMin/+ These mice were from The Jackson Laboratory.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

observed
C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon tumor
  • chenodeoxycholate (chenodeoxycholic acid)
 Intestine - Large Intestine - Colon

observed
C57BL/6J Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

0
C57BL/6J-ApcMin/+ Intestine - Small Intestine - Duodenum tumor Intestine - Small Intestine - Duodenum

observed
C57BL/6J-ApcMin/+ Intestine - Small Intestine - Duodenum tumor
  • chenodeoxycholate (chenodeoxycholic acid)
 Intestine - Small Intestine - Duodenum

observed
C57BL/6J Intestine - Small Intestine - Duodenum tumor Intestine - Small Intestine - Duodenum

0
C57BL/6J-ApcMin/+ Intestine - Small Intestine tumor Intestine - Small Intestine

observed
C57BL/6J-ApcMin/+ Intestine - Small Intestine tumor
  • chenodeoxycholate (chenodeoxycholic acid)
 Intestine - Small Intestine

observed
C57BL/6J Intestine - Small Intestine tumor Intestine - Small Intestine

0