Journal Article

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

Najjia N. Mahmoud, Andrew J. Dannenberg, Robyn T. Bilinski, Juan R. Mestre, Amy Chadburn, Matthew Churchill, Charles Martucci and Monica M. Bertagnolli

in Carcinogenesis

Volume 20, issue 2, pages 299-303
Published in print February 1999 | ISSN: 0143-3334
Published online February 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.2.299
Administration of an unconjugated bile acid increases duodenal tumors in a murine model of familial adenomatous polyposis

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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 β-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 β-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.

Keywords: Cox-2, cyclooxygenase-2; FAP, familial adenomatous polyposis; Min/+, C57BL/6J-Min/+; PCNA, proliferating cell nuclear antigen; PGE2, prostaglandin E2; PBS, phosphate-buffered saline; TUNEL, terminal deoxynucleotide nick end labeling.

Journal Article.  4320 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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