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L-Ascorbic Acid Amplification of Bladder Carcinogenesis Promotion by K₂CO₃¹

First Department of Pathology, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467, Japan

The dose dependence of K₂CO₃ promotion of two-stage urinary bladder carcinogenesis and the amplifying effects of additional L-ascorbic acid (AsA) administration were investigated. Male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks and then fed basal diet containing K₂CO₃ at levels of 0, 1, 1.5, 2.2, and 3% with or without 5% AsA or 3% NaHCO₃ supplementation from weeks 5 to 8 (4 weeks) and weeks 12 to 20 (9 weeks). During weeks 9 to 11 (3 weeks), the rats were fed 3% uracil in their diet. For controls, rats without N-butyl-N-(4-hydroxybutyl)nitrosamine treatment were given either 3% K₂CO₃, 5% AsA, or both plus the uracil treatment. The total observation period was 20 weeks. K₂CO₃ dose dependently increased the numbers of the putative preneoplastic lesion, papillary or nodular hyperplasia, and papillomas in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine. AsA (5%), while itself exerting no promoting effect, amplified the enhancing influence of K₂CO₃ on the induction of papillary or nodular hyperplasia and papillomas. The dose-dependent elevation of urinary pH and K⁺ concentration was associated with K₂CO₃ treatment with or without AsA. Thus, increased urinary pH and K⁺ concentration appear to play important roles in K₂CO₃ promotion, and AsA amplifies this promotion.

¹ This study was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture of Japan and from the Ministry of Health and Welfare of Japan and by a grant from the Society for Promotion of Pathology of Nagoya.

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

Received 9/21/90. Accepted 3/ 5/91.