title: Acid has antiproliferative effects in nonneoplastic Barrett's epithelial cells.
abstract: OBJECTIVE
  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.affiliation: Department of Medicine, Dallas VA Medical Center, University of Texas-Southwestern Medical School, Dallas, Texas 75216, USA.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Feagins
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Zhang
authors.forename: Kathy
authors.initials: K
authors.lastname: Hormi-Carver
authors.forename: Mizael H
authors.initials: MH
authors.lastname: Quinones
authors.forename: Deena
authors.initials: D
authors.lastname: Thomas
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Lance S
authors.initials: LS
authors.lastname: Terada
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Spechler
authors.forename: Ruben D
authors.initials: RD
authors.lastname: Ramirez
authors.forename: Rhonda F
authors.initials: RF
authors.lastname: Souza
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D006851:Hydrochloric Acid / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D006851:Hydrochloric Acid