Original Article
Molecular effects of tobacco smoke and bile reflux in Barrett’s esophagus in vitro
Abstract
Background: Chronic gastroesophageal-reflux disease creates an environment of high oxidative stress believed to contribute to the carcinogenic transformation from reflux esophagitis to the premalignant condition Barrett’s esophagus (BE). BE ultimately progresses to esophageal adenocarcinoma (EAC). The aim of this study was to confirm the molecular effects of tobacco smoke and bile reflux in the molecular carcinogenesis of Barrett’s adenocarcinoma.
Methods: Tobacco smoke condensate (4,000 ng/mL and dilutions) and a standardized bile acid (0.4 mM) were used to determine effects on a human hTERT-immortalized non-neoplastic Barrett’s esophageal cell line (BarT) and a human esophageal squamous cell line (Het-1a). Fourteen clinically relevant genes were evaluated via relative quantification real-time PCR analysis.
Results: There was a synergistic relationship regarding the effects of bile acids and smoke condensate on both the BarT and Het-1a cell lines. Genes for inflammatory mediators COX2, IL1β, IL6, and IL8 were significantly up-regulated by combination smoke and bile treatment in both cell lines, while genes vital for cellular protection such as superoxide dismutase genes, MUC family of genes, CDX2 and CYP3A4 had varying expression changes.
Conclusions: Tobacco smoke may enhance harmful effects of bile-acid refluxate on esophageal mucosa and is a significant factor in EAC carcinogenesis.
Methods: Tobacco smoke condensate (4,000 ng/mL and dilutions) and a standardized bile acid (0.4 mM) were used to determine effects on a human hTERT-immortalized non-neoplastic Barrett’s esophageal cell line (BarT) and a human esophageal squamous cell line (Het-1a). Fourteen clinically relevant genes were evaluated via relative quantification real-time PCR analysis.
Results: There was a synergistic relationship regarding the effects of bile acids and smoke condensate on both the BarT and Het-1a cell lines. Genes for inflammatory mediators COX2, IL1β, IL6, and IL8 were significantly up-regulated by combination smoke and bile treatment in both cell lines, while genes vital for cellular protection such as superoxide dismutase genes, MUC family of genes, CDX2 and CYP3A4 had varying expression changes.
Conclusions: Tobacco smoke may enhance harmful effects of bile-acid refluxate on esophageal mucosa and is a significant factor in EAC carcinogenesis.
