Acute acid exposure increases rabbit esophageal cell proliferation

In the present study we examined whether an acute infusion of HCl into the esophagus of rabbits would cause an increase in esophageal cellular proliferation independent of morphologic evidence of cell injury. To examine this question, the distal two thirds of the rabbit esophagus was infused for 1 hour with either 40 mmol/L HCl or NSS (control), and cellular proliferation was studied 24 and 48 hours later by using bromodeoxyuridine (BrDu) to label the nuclei of dividing cells and ornithine decarboxylase (ODC) enzyme activity as a biochemical index of cell division, Although there was no gross or microscopic evidence of cell necrosis or mucosal inflammation 24 hours after H+ infusion, BrDu labeling of basal cell nuclei was significantly greater 24 hours after H+ infusion (31% +/- 6%) as compared with that in control animals infused with NSS (15% +/- 4%), This increase in labeling index was paralleled by a threefold greater ODC enzyme activity at 24 hours with H+ infusion. Rete pegs were infrequent in control tissues (4 +/- 4 rete pegs per 100 mu m of esophageal length) or in animals examined 24 hours after acid exposure (4 +/- 2 rete pegs per 100 Irm) However, rete pegs were very prominent 48 hours after acid infusion (22 +/- 6 rete pegs per 100 mu m). A short exposure to acid can cause a significant increase in mucosal proliferation independent of injury, suggesting that esophageal cell acidification either directly or indirectly acts as a tissue mitogen.