ArticleGut2010
A novel mechanism of acid and bile acid-induced DNA damage involving Na+/H+ exchanger: implication for Barrett's oesophagus.
Article in Gut, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 65 citations in OpenAlex.
- NHE1 in Gastrointestinal Inflammation and Cancer: A Double-Edged Regulator.Digestive diseases and sciences · 2026Review
- A TRIM15-CDX2 loop drives bile acid-induced gastric intestinal metaplasia.Molecular medicine (Cambridge, Mass.) · 2026Article
- Increased reflux secondary bile acids are associated with changes to the microbiome and transcriptome in Barrett's esophagus.Gut microbes · 2025Article
- Prebiotic proanthocyanidins inhibit bile reflux-induced esophageal adenocarcinoma through reshaping the gut microbiome and esophageal metabolome.JCI insight · 2024Article
- Current study of pathogenetic mechanisms and therapeutics of chronic atrophic gastritis: a comprehensive review.Frontiers in cell and developmental biology · 2024Review
- Cranberry Proanthocyanidins Mitigate Reflux-Induced Transporter Dysregulation in an Esophageal Adenocarcinoma Model.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Diagnostic Principles for Chronic Gastritis Associated with Duodenogastric Reflux.Diagnostics (Basel, Switzerland) · 2023Review
- Increased PXR and Suppressed T-Cell Signaling Are Associated With Malignant Degeneration of Barrett's Esophagus.Gastro hep advances · 2023Article
- Decreased NHE3 expression in colon cancer is associated with DNA damage, increased inflammation and tumor growth.Scientific reports · 2022Article
- Article
- Elevation of fatty acid desaturase 2 in esophageal adenocarcinoma increases polyunsaturated lipids and may exacerbate bile acid-induced DNA damage.Clinical and translational medicine · 2022Article
- Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review.Cell death discovery · 2022Review
- Primary bile acid activates Egr‑1 expression through the MAPK signaling pathway in gastric cancer.Molecular medicine reports · 2022Article
- Article
- Bile reflux and hypopharyngeal cancer (Review).Oncology reports · 2021Review
- Inhibition of NHE-1 Increases Smoke-Induced Proliferative Activity of Barrett's Esophageal Cell Line.International journal of molecular sciences · 2021Article
- Advances in research on the regulatory mechanism of NHE1 in tumors.Oncology letters · 2021Review
- OEsophageal Ion Transport Mechanisms and Significance Under Pathological Conditions.Frontiers in physiology · 2020Review
- Activin A-mediated epithelial de-differentiation contributes to injury repair in an in vitro gastrointestinal reflux model.Cytokine · 2019Article
- (Patho-)Physiology of NaFrontiers in physiology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectiveBarrett's oesophagus is a premalignant disease associated with oesophageal adenocarcinoma. The major goal of this study was to determine the mechanism responsible for bile acid-induced alteration in intracellular pH (pH(i)) and its effect on DNA damage in cells derived from normal oesophagus (HET1A) or Barrett's oesophagus (CP-A).
designCells were exposed to bile acid cocktail (BA) and/or acid in the presence/absence of inhibitors of nitric oxide synthase (NOS) or sodium-hydrogen exchanger (NHE). Nitric oxide (NO), pH(i) and DNA damage were measured by fluorescent imaging and comet assay. Expression of NHE1 and NOS in cultured cells and biopsies from Barrett's oesophagus or normal squamous epithelium was determined by RT-PCR, immunoblotting or immunohistochemistry.
resultsA dose dependent decrease in pH(i) was observed in CP-A cells exposed to BA. This effect of BA is the consequence of NOS activation and increased NO production, which leads to NHE inhibition. Exposure of oesophageal cells to acid in combination with BA synergistically decreased pH(i). The decrease was more pronounced in CP-A cells and resulted in >2-fold increase in DNA damage compared to acid treatment alone. Examination of biopsies and cell lines revealed robust expression of NHE1 in Barrett's oesophagus but an absence of NHE1 in normal epithelium.
conclusionsThe results of this study identify a new mechanism of bile acid-induced DNA damage. We found that bile acids present in the refluxate activate immediately all three isoforms of NOS, which leads to an increased NO production and NHE inhibition. This consequently results in increased intracellular acidification and DNA damage, which may lead to mutations and cancer progression. Therefore, we propose that in addition to gastric reflux, bile reflux should be controlled in patients with Barrett's oesophagus.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.