Rapid Induction of Hyperplasiain Vitroin Rat Bladder Explants by Elevated Sodium Ion Concentrations and Alkaline pH

Abstract

The effects of alkaline pH and elevated sodium concentrations in culture medium on rat bladder explants for 1, 2, and 3 weeks were investigated by continuous BrdU labeling and histopathology. Increasing the sodium chloride concentration of normal medium by 50 or 100 mMcaused slight urothelial hyperplasia with statistically significant increases in labeling in week 2 (50 mM) and at all time points with 100 mMNaCl. Cytotoxicity was seen in the high salt group. Increasing the pH from 7.2 to 7.8 and 8.2 also caused a slight hyperplastic response with significant increases in labeling and cytotoxicity at pH 8.2. However, bladder explants treated at pH 7.8 or 8.2 with excess sodium concentrations of 50 to 100 mMhad a more marked hyperplastic response with evidence of cytotoxicity as well. There were significant increases in the labeling index (6.4- to 15.0-fold relative to control) after 1 week, with the maximum response at 100 mMsodium/pH 8.2. These results suggest that alkaline pH and elevated sodium concentration have a direct mitogenic effect on rat urothelial cells with some cytotoxicity-induced regenerative cell proliferation as well. Thesein vitroresults in an organ culture system are in agreement within vivostudies that have shown an important role for elevated urinary cation concentrations and pH in the stimulation of DNA synthesis, induction of hyperplasia, and tumor promotion in rat bladder epithelium.