Darragh, J.; Ross, P.E.; Dillon, J.F.; Kernohan, N.M.; Dettmar, P.W.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA7
Academic Journal
Aim: Bile acids are one component of gastric contents that can reflux into the oesophagus in patients with GORD. Bile acids have been shown to induce apoptosis in colonic epithelium and hepatocytes. Similar activity on oesophageal epithelium may contribute to the pathogenesis of GORD. As the effect of bile acids on the oesophagus has not been examined in detail we have investigated the effects of bile acids on apoptosis of established oesophageal cell lines. Methods: Oesophageal cell lines (OE19, OE21, OE33, and KYSE30), a wild type p53 colon cell line (HCT116), and it's derived isogenic p53 null cell line were grown in medium containing different biochemically pure bile acids. Apoptosis was identified by cell morphology, the presence of sub G1 DNA fragments by flow cytometry and detection of activated caspase-3 by Western blot. Results: OE 33 and OE 19 (derived from an adenocarcinoma) exhibited a dose dependent induction of apoptosis in response to deoxycholic acid (DCA) and chenoDCA. The cell lines derived From squamous cancers (OE21 and KYSE30) were resistant to the proapoptotic effect of bile acids. Less hydrophobic bile acids, such as cholic acid and tauroDCA were unable to induce apoptosis. Caspase 3 activation was observed in apoptotic ceils, however p53 protein levels remained unaffected. The proapoptotic activity of DCA was p53 independent, both p53 wild type and null isogenic colonic cell lines being equally sensitive. Conclusion: DCA and chenoDCA induce p53 independent apoptosis in some oesophageal cell lines, although those that exhibit squamous differentiation are resistant. The proapoptotic activity of particular bile acids may contribute to mucosal damage. Our results also suggest that this response may compensate for loss of p53 activity that occurs in oesophageal cancers and that loss of this bile acid induced effect in vivo may favour tumour.


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