Document Detail


Acid has antiproliferative effects in nonneoplastic Barrett's epithelial cells.
MedLine Citation:
PMID:  17266684     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: For patients with Barrett's esophagus, physicians commonly prescribe antisecretory medications in dosages above those required to heal reflux esophagitis because acid has been shown to have proproliferative and antiapoptotic effects on Barrett's cancer cells and on Barrett's mucosal explants. For a number of reasons, these model systems may not be ideal for determining the effects of acid on benign Barrett's epithelial cells, however. We studied the effects of acid on proliferation and apoptosis in a nonneoplastic, telomerase-immortalized Barrett's epithelial cell line. METHODS: Barrett's cells were treated with two 3-minute exposures to acidic media. Cell growth was determined using cell counts, proliferation was studied by flow cytometry, cell viability was determined by trypan blue staining, and apoptosis was assessed by TUNEL and Annexin V. The expression levels of p53 and p21 were determined by Western blotting. p53 siRNA was used to study the effect of p53 inhibition on total cell numbers after acid exposure. RESULTS: Acid exposure significantly decreased total cell numbers at 24 h without affecting either cell viability or apoptosis. Acid exposure resulted in cell cycle prolongation that was associated with greater expression of p53, but not p21. The acid-induced decrease in total cell numbers was abolished by p53 RNAi. CONCLUSIONS: Acid exposure has p53-mediated, antiproliferative effects in nonneoplastic Barrett's epithelial cells. These findings contradict the results of prior in vitro and ex vivo studies. We speculate that the prescription of antisecretory medications in dosages beyond those required to heal gastroesophageal reflux disease (GERD) symptoms and endoscopic signs could be detrimental. Controlled, prospective clinical trials are needed to determine the optimal level of acid suppression for patients with Barrett's esophagus.
Authors:
Linda A Feagins; Hui-Ying Zhang; Kathy Hormi-Carver; Mizael H Quinones; Deena Thomas; Xi Zhang; Lance S Terada; Stuart J Spechler; Ruben D Ramirez; Rhonda F Souza
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The American journal of gastroenterology     Volume:  102     ISSN:  0002-9270     ISO Abbreviation:  Am. J. Gastroenterol.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-02-01     Completed Date:  2007-03-16     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  0421030     Medline TA:  Am J Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10-20     Citation Subset:  IM    
Affiliation:
Department of Medicine, Dallas VA Medical Center, University of Texas-Southwestern Medical School, Dallas, Texas 75216, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Apoptosis / drug effects
Barrett Esophagus / metabolism*,  pathology
Blotting, Western
Cell Count
Cell Division / drug effects
Cell Line
Cell Survival / drug effects
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Flow Cytometry
Humans
Hydrochloric Acid / pharmacology*
In Situ Nick-End Labeling
Tumor Suppressor Protein p53 / metabolism
Ultraviolet Rays
Grant Support
ID/Acronym/Agency:
5T32DK-07745/DK/NIDDK NIH HHS; DK63621/DK/NIDDK NIH HHS; HL61897/HL/NHLBI NIH HHS; HL67256/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p21; 0/Tumor Suppressor Protein p53; 7647-01-0/Hydrochloric Acid
Comments/Corrections
Comment In:
Am J Gastroenterol. 2007 Jan;102(1):21-3   [PMID:  17266685 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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