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L-Ascorbic Acid Amplification of Second-Stage Bladder Carcinogenesis Promotion by NaHCO₃¹

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

The dose dependence of NaHCO₃ promotion of urinary bladder carcinogenesis and the effects of additional L-ascorbic acid (AsA) administration were investigated subsequent to initiation. Male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks and then, starting 3 days after cessation of carcinogen treatment, received basal diet containing NaHCO₃ at levels of 0, 0.375, 0.75, 1.5, and 3.0% with or without a 5% AsA supplement for 32 weeks. NaHCO₃ dose-dependently increased the incidence and numbers of urinary bladder carcinomas in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine. 5% AsA, while itself exerting no promoting effect, amplified the enhancing influence of NaHCO₃ on induction of urinary bladder carcinomas. The same dose-dependent elevation of urinary pH and Na⁺ concentration was associated with NaHCO₃ treatment with or without AsA. NaHCO₃ significantly increased DNA synthesis in the urinary bladder epithelium and the additional treatment with AsA was associated with a significant further elevation. Thus, increased urinary pH and Na⁺ concentrations appear to play important roles in NaHCO₃ promotion and AsA amplified this promotion. NaHCO₃ treatment, with or without AsA, induced cellular proliferation, although it is unclear whether this is an essential factor.

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; by a Grant-in-Aid from the Ministry of Health and Welfare for a Comprehensive 10-Year Strategy for Cancer Control; and by the Society for Promotion of Pathology, Nagoya, Japan.

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

Received 4/ 4/88. Revised 8/12/88. Accepted 8/17/88.

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