Effects of urinary potassium and sodium ion concentrations and pH on N-butyl-N(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in rats

Abstract

The promoting activities of low and high sodium or potassium ion concentrations, under conditions of neutral as well as elevated urinary pH, in urinary bladder carcinogenesis, were investigated in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Male Wistar rats were given 0.05% BBN in their drinking water for 4 weeks and then treated for 32 weeks with either control diet (group 1) or this diet supplemented with equimolar amounts of the following minerals: 2.34% NaCl (group 2), 2.98% KCl (group 3), 3.36% NaHCO3 (group 4), 1.68% NaHCO3 + 2% KHCO3 (group 5), or 4% KHCO3 (group 6). The alkalizing salts NaHCO3 and KHCO3 induced comparable increases in urinary pH and elevated urinary sodium or potassium ion concentrations respectively. The combination of NaHCO3 + KHCO3 similarly caused an elevation of the urinary pH and less increased sodium and potassium ion concentrations. In the groups fed NaHCO3 and KHCO3 either alone or in combination, the incidences of papillary/nodular hyperplasia, papillomas and carcinomas in the urinary bladder had increased as compared to controls. NaCl and KCl also induced high urinary sodium or potassium ion concentrations without alteration of urinary pH. This was accompanied by increased incidences of simple hyperplasia, papillary/nodular hyperplasia, and/or papillomas but no carcinomas. The present results indicate that the potassium ion is as potent as the sodium ion in promoting urinary bladder carcinogenesis under conditions of elevated urinary pH, and that both the sodium and potassium ions may exert weak promoting activity under conditions of neutral urinary pH.