Mechanisms of oxidant production in esophageal squamous cell and Barrett's cell lines

Am J Physiol Gastrointest Liver Physiol. 2008 Feb;294(2):G411-7. doi: 10.1152/ajpgi.00373.2007. Epub 2007 Dec 6.


We hypothesized that differences among individuals in reflux-induced oxidant production by esophageal squamous epithelial cells might contribute to the development of Barrett's esophagus. We studied the effects of acid and bile acids on the production of reactive oxygen species (ROS) in esophageal squamous cell lines derived from gastroesophageal reflux disease patients with (NES-B3T) and without (NES-G2T) Barrett's esophagus and in a Barrett's epithelial cell line (BAR-T). Cells were incubated with an ROS-sensitive probe and exposed to acidic medium, neutral bile acid medium, or acidic bile acid medium. ROS were quantified in the presence and absence of diphenyleneiodonium chloride (DPI, an NADPH oxidase inhibitor), N(G)-monomethyl-l-arginine (l-NMMA, a nitric oxide synthase inhibitor), and rotenone (a mitochondrial electron transport chain inhibitor). Acidic bile acid medium induced ROS production in both squamous cell lines; however, only DPI blocked ROS production by NES-B3T cells, whereas both DPI and l-NMMA blocked ROS production by NES-G2T cells. In BAR-T cells, acidic medium and acidic bile acid medium induced the production of ROS; l-NMMA prevented ROS production after exposure to acidic medium, whereas ROS production induced by acidic bile acid medium was blocked by DPI. These studies demonstrate that there are differences between esophageal squamous cells and Barrett's epithelial cells and between esophageal squamous cells from gastroesophageal reflux disease patients with and without Barrett's esophagus in the mechanisms of oxidant production induced by exposure to acid and bile acids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Barrett Esophagus / metabolism*
  • Barrett Esophagus / pathology*
  • Bile Acids and Salts / pharmacology
  • Cell Line
  • Cell Line, Tumor
  • Culture Media
  • Enzyme Inhibitors / pharmacology
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Esophagus / cytology
  • Esophagus / metabolism*
  • Esophagus / pathology
  • Gastroesophageal Reflux / pathology
  • Humans
  • NADPH Oxidases / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Oxidants / metabolism*
  • Reactive Oxygen Species / metabolism
  • Telomerase / metabolism
  • omega-N-Methylarginine / pharmacology


  • Bile Acids and Salts
  • Culture Media
  • Enzyme Inhibitors
  • Oxidants
  • Reactive Oxygen Species
  • omega-N-Methylarginine
  • Nitric Oxide Synthase
  • NADPH Oxidases
  • Telomerase