Significance of L-ascorbic acid and urinary electrolytes in promotion of rat bladder carcinogenesis.

The present studies report on the significance of L-ascorbic acid (AA) and urinary electrolytes for promotion of rat urinary bladder carcinogenesis. Male F344 rats were given an oral administration of 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as an initiator for 4 weeks, and were then subjected to treatment with dietary supplements of test chemicals for 32 weeks. Administration of 5% sodium L-ascorbate (SA), the sodium ion form of AA significantly promoted urinary bladder carcinogenesis, whereas administration of 5% AA did not. The urine of rats given SA but not AA was characterized by an apparent elevation of pH, an increase of sodium ion concentration, and increases in the urinary content of total AA and its metabolite, dehydroascorbic acid. Administration of 3% NaHCO3, which induced elevation of pH and increase of sodium ion concentration in the urine, promoted BBN bladder carcinogenesis. When rats were given 5% AA plus 3% NaHCO3, AA enhanced the promoting activity of NaHCO3. Lowering of pH by 1% NH4Cl clearly reduced the promoting activity of 5% SA when these two compounds were given concurrently. Treatment with 5% AA plus 3% K2CO3 promoted BBN bladder carcinogenesis in rats, whereas addition of 5% CaCO3 or 5% MgCO3 to AA did not. These results strongly indicate the important role of urinary sodium or potassium ion concentration and pH in modulating urinary bladder carcinogenesis by AA.