Acid has antiproliferative effects in nonneoplastic Barrett's epithelial cells.
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.
Feagins
Linda A
LA
Department of Medicine, Dallas VA Medical Center, University of Texas-Southwestern Medical School, Dallas, Texas 75216, USA.
Zhang
Hui-Ying
HY
Hormi-Carver
Kathy
K
Quinones
Mizael H
MH
Thomas
Deena
D
Zhang
Xi
X
Terada
Lance S
LS
Spechler
Stuart J
SJ
Ramirez
Ruben D
RD
Souza
Rhonda F
RF
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
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D006851:Hydrochloric Acid