The role of urinary pH and sodium ion concentration in the promotion stage of two-stage carcinogenesis of the rat urinary bladder.

The promoting activities of NaHCO3 and NaCl in two-stage urinary bladder carcinogenesis in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated. Male F344 rats were given 0.05% BBN in their drinking water for 4 weeks and then treated with basal diet containing either 3% NaHCO3, 1% NaCl or no added chemical for 32 weeks. NaHCO3 significantly increased the induction of neoplastic and preneoplastic lesions of the urinary bladder, whereas NaCl did not. NaHCO3 produced elevation of urinary pH and urinary Na+ concentration. NaCl increased urinary Na+ concentration without the elevation of urinary pH. In an additional experiment, DNA synthesis in the urinary bladder epithelium was significantly increased in the groups given 3% NaHCO3, 5% sodium L-ascorbate and 1% NaCl. These results confirm that urinary components, increase in urinary pH and Na+ concentration play an important role in the promotion of urinary bladder carcinogenesis in rats.