Mutagenesis vol. 19 no. 4 pp. 319-324,
July 2004
© 2004 UK Environmental Mutagen Society/Oxford University Press
Acid and bile salts induce DNA damage in human oesophageal cell lines
Molecular Epidemiology Unit, School of Medicine, Epidemiology and Health Services Research, Algernon Firth Building, University of Leeds, Leeds LS2 9JT, UK
Barrett’s oesophagus is an acquired precancerous condition that develops from mucosal injury incurred due to chronic gastro-oesophageal reflux. The aim of this study was to determine if bile and/or acid components of the refluxate can induce DNA damage in vitro. The oesophageal cell lines FLO-1 and HET1-A were exposed to primary bile salts, individually or as a mixture, and the secondary bile salt sodium deoxycholate, in neutral or acidified media. Cells were then examined in the comet assay to measure DNA strand breaks. Cell viability was also monitored. Acidified media induced DNA damage in a pH- and time-dependent manner. The primary bile compounds sodium glycocholate, glycocholic acid, sodium taurocholate and taurochenodeoxycholate, as an equimolar mixture (100 µM), caused a small but significant (P < 0.028) elevation in DNA damage, but only at neutral pH in FLO-1 cells. Sodium deoxycholate (100 µM) caused a significant (P < 0.008) elevation in DNA damage in both cell lines, but again only at neutral pH. These data suggest that specific components of gastro-oesophageal refluxate are capable of causing DNA damage and may participate in the genesis and progression of Barrett’s oesophagus via this mechanism.
1To whom correspondence should be addressed. Tel: +44 113 343 6593; Fax: +44 113 343 6603; Email: medljh{at}leeds.ac.uk
Received on February 4, 2004; revised on April 22, 2004; accepted on April 26, 2004
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