Participation of urinary Na +, K +, pH, and L-ascorbic acid in the proliferative response of the bladder epithelium after the oral administration of various salts and/or ascorbic acid to rats

Abstract

Changes in urinary parameters (particularly electrolyte levels and pH), and DNA synthesis and the morphology of the bladder epithelium were investigated in rats that were fed for 4 or 8 wk on diets containing various Na, K, Mg or Ca carbonate salts, with or without l-ascorbic acid (AsA). [The carbonate salts were fed at a level of 3% in the diet, and AsA or AsA-Na was administered at 5% in the diet. NH 4Cl was at 1% in the diet.] The effects of treatment with NH 4Cl (used as a urine acidifier), and of combined treatment with sodium ascorbate (AsA-Na) and NH 4Cl were also investigated. Urinary pH was significantly elevated in groups given NaHCO 3, K 2CO 3, AsA + NaHCO 3, AsA + K 2CO 3 and AsA-Na, whereas treatment with AsA or NH 4Cl alone caused a significant drop in urinary pH. An increase in urinary electrolytes or ascorbic acid was associated with the corresponding dosing regimen. DNA synthesis in the bladder epithelium was increased in groups given NaHCO 3, K 2CO 3, AsA + NaHCO 2, AsA + K 2CO 3 or AsA-Na. Furthermore, all treatments that induced an elevation of DNA synthesis also induced some morphological alterations in the bladder epithelium. The administration of AsA in conjunction with NaHCO 3 or K 2CO 3 induced levels of change greater than those with either salt alone. In contrast, the degree of response in the bladder epithelium of rats given AsA-Na was reduced by the simultaneous administration of NH 4Cl. These results suggest that the degree of DNA synthesis and/or morphological alteration in the rat-bladder epithelium after treatment with various bases may depend on changes in urinary concentrations of Na + or K + ions and/or pH, and the presence of ascorbic acid in the urine. The results are discussed in relation to the possible promotion by various treatment regimens (salts ± AsA) of urinary bladder carcinogenesis.