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Roles of Urinary Sodium Ion Concentration and pH in Promotion by Ascorbic Acid of Urinary Bladder Carcinogenesis in Rats¹

First Department of Pathology, Nagoya City University Medical School, Mizuho-ku, Nagoya 467, Japan

Since the sodium salt of ascorbic acid (AA) promoted two-stage urinary bladder carcinogenesis in rats, whereas AA itself did not, the roles of the urinary sodium ion concentration and pH on urinary bladder carcinogenesis were investigated. Male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks and then treated with basal diet containing 5% AA plus 3% sodium bicarbonate (NaHCO₃), 5% AA, 3% NaHCO₃ or 5% sodium L-ascorbate (SA), 5% SA plus 1% ammonium chloride (NH₄Cl) or 1% NH₄Cl, or no added chemical for 32 weeks. NaHCO₃ significantly increased the induction of neoplastic and preneoplastic lesions of the urinary bladder. Like SA, AA plus NaHCO₃ induced high incidences of neoplastic and preneoplastic lesions of the urinary bladder, whereas AA alone did not. NH₄Cl reduced the promoting activity of SA in urinary bladder carcinogenesis. These results suggest important roles for urinary sodium ion concentration and pH in modulating urinary bladder carcinogenesis. Moreover, AA was found to act as a copromoter under conditions of increased urinary pH and sodium ion concentration.

¹ This work was supported by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture and the Ministry of Health and Welfare of Japan and by a Grant-in-Aid from the Ministry of Health and Welfare for a Comprehensive 10 Year Strategy for Cancer Control, Japan.

² To whom requests for reprints should be addressed, at the First Department of Pathology, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467, Japan.

Received 8/22/85. Revised 12/17/85. Accepted 12/18/85.