Jolly A J, Wild C P, Hardie L J
Molecular Epidemiology Unit, School of Medicine, Epidemiology and Health Services Research, Algernon Firth Building, University of Leeds, Leeds LS2 9JT, UK.
Mutagenesis. 2004 Jul;19(4):319-24. doi: 10.1093/mutage/geh035.
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 microM), caused a small but significant (P < 0.028) elevation in DNA damage, but only at neutral pH in FLO-1 cells. Sodium deoxycholate (100 microM) 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.
巴雷特食管是一种后天性癌前病变，由慢性胃食管反流引起的黏膜损伤发展而来。本研究的目的是确定反流物中的胆汁和/或酸成分是否能在体外诱导DNA损伤。将食管细胞系FLO-1和HET1-A分别或混合暴露于初级胆汁盐以及次级胆汁盐脱氧胆酸钠中，培养基为中性或酸化培养基。然后通过彗星试验检测细胞以测量DNA链断裂情况。同时监测细胞活力。酸化培养基以pH值和时间依赖性方式诱导DNA损伤。初级胆汁化合物甘氨胆酸钠、甘胆酸、牛磺胆酸钠和牛磺鹅去氧胆酸以等摩尔混合物（100微摩尔）形式存在时，会使DNA损伤略有但显著升高（P < 0.028），但仅在FLO-1细胞的中性pH条件下。脱氧胆酸钠（100微摩尔）在两种细胞系中均导致DNA损伤显著升高（P < 0.008），同样仅在中性pH条件下。这些数据表明，胃食管反流物的特定成分能够导致DNA损伤，并可能通过这种机制参与巴雷特食管的发生和发展。
