Bile salts induce or blunt cell proliferation in Barrett's esophagus in anacid-dependent fashion

Barrett's esophagus (BE) results from acid and bile reflux and predisposes to cancer. We investigated the effect of bile salts, with or without acid, on cell proliferation in BE and assessed mechanism(s) involved. To mimic ph ysiological conditions, biopsies of esophagus, BE, and duodenum were expose d to a bile salt mixture, either continuously or as a 1-h pulse, and were c ompared with control media without bile salts (pH 7.4) for less than or equ al to 24 h. Similar experiments were also performed with acidified media (p H 3.5) combined with the bile salt mixture as a 1-h pulse. Cell proliferati on was assessed by a [H-3]thymidine incorporation assay with or without bis indolylmaleimide (BIM), a selective protein kinase C inhibitor. Bile salt p ulses enhanced cell proliferation in BE without affecting cell proliferatio n in esophageal or duodenal epithelia. In the presence of BIM, there was co mplete obliteration of the bile salt-induced BE hyperproliferation. In cont rast, 1-h pulses of bile salts in combination with acid significantly inhib ited proliferation in BE but had no effect on esophagus or duodenum. We con clude that in BE explants, brief exposure to bile salts, in the absence of acid, increases proliferation, whereas exposure to a combination of bile sa lts and acid together inhibits proliferation.