Carcinogenesis, Vol. 20, No. 2, 299-303,
February 1999
© 1999 Oxford University Press
Administration of an unconjugated bile acid increases duodenal tumors in a murine model of familial adenomatous polyposis
1 The New York Hospital-Cornell University Medical Center, 525 East 68th Street, New York, NY 10021 and
2 Strang Cancer Prevention Center, 428 East 72nd Street, New York, NY 10021, USA
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 ß-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 ß-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.
Abbreviations: 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.
3 To whom correspondence should be addressed Email: mbertagn{at}mail.med.cornell.edu
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