D'souza], F.R.; Jenkins, G.J.; Parry, E.M.; Baxter, J.N.; Parry, J.M.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA47
Academic Journal
Background/Aims: The incidence of adenocarcinoma of the oesophagus has rapidly increased over the past few decades. Virtually all adenocarcinomas arise in Barrett's oesophagus (BE), the exact aetiology of which is still unknown. There is increasing evidence that bile acids play a significant role in the pathogenesis of BE. Studies have shown that patients with BE have increased bile reflux compared to patients with uncomplicated gastro-oesophageal reflux. Effects of bile acids on oesophageal cell lines have not been previously demonstrated. Our study aimed at the evaluation of genotoxic potential of physiological concentrations of bile acids on oesophageal cell lines. Methods: OE33 cells were purchased from ECACC (European Collection of Cell Cultures). Six different bile acids, namely Taurocholic acid (TCA), Glycocholic acid (GCA), Taurodeoxycholic acid (TDCA), Glycodeoxycholic acid (GDCA), Deoxycholic acid (DCA) and Cholic acid (CA) were used in near physiological concentrations ranging from 50µmol-1 mmol. The Cytokinesis Blocked In-vitro Micronucleus Assay, a well accepted genotoxicity assay, was used to assess both structural and numerical chromosomal damage. Kinetochore labelling was performed to distinguish aneugens from clastogens. Apoptosis and necrosis was measured based on the morphological criteria. Results: All the bile acids induced cytotoxicity in a dose dependent manner. The un-conjugated bile acids (DCA & CA) were more cytotoxic than the conjugated bile acids (TCA, GCA, TDCA, & GDCA). None of the bile acids except DCA showed any significant induction of micronuclei. DCA induced a statistically significant increase in the frequency of micronucleus in comparison with normal control (42 v 14 micronuclei/2000 cells, p=0.0029, Fisher exact test). DCA was predominantly clastogenic in action as revealed by the kinetochore labelling (66% kinetochore positive and 34% kinetochore negative). DCA also induced significant apoptosis (21 v 3/500...


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