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Toxicologic Pathology, Vol. 33, No. 7, 766-769 (2005)
DOI: 10.1080/01926230500416336

Articles

Lack of Urinary Bladder Carcinogenicity of Sodium L-Ascorbate in Human c-Ha-ras Proto-Oncogene Transgenic Rats

Keiichirou Morimura1, Jin Seok Kang1, Min Wei1, Hideki Wanibuchi1, Hiroyuki Tsuda2 and Shoji Fukushima1

1 Department of Pathology, Osaka City University Medical School, Osaka, Japan
2 Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Correspondence: Address correspondence to: Shoji Fukushima, Prof. and Chairman, Department of Pathology, Osaka City University Medical School, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan; e-mail:fukuchan{at}med.osaka-cu.ac.jp

Sodium L-ascorbate (Na-AsA) is widely known to be a tumor promoter of rat bladder carcinogenesis but tests negative in standard 2-year bioassays. In the present study, bladder-cancer-susceptible transgenic rats designated Hras128 were used to further examine the tumorigenicity of Na-AsA. A total of 40 7-week-old male transgenic (Tg) and 42 littermate nontransgenic (Non-tg) rats were divided into 4 groups and given powdered MF diet with or without 5% Na-AsA for 57 weeks. Tg rats showed significantly short survival compared with Non-tg, independent of Na-AsA treatment. Tg rats treated with Na-AsA showed a slightly higher incidence of carcinoma (29.6%) as compared to those without Na-AsA treatment (15.4%), but this was without statistical significance. Moreover, the total bladder tumor incidences, including papillomas, did not differ statistically (with Na-AsA, 37.0%; without Na-AsA, 30.8%). No bladder tumor was detected in Non-tg rats. Various kinds of other lesions in various organs were noted in Tg rats treated with or without Na-AsA treatment, but no intergroup differences were evident. In conclusion, Na-AsA did not show tumorigenicity in highly bladder-cancer-susceptible transgenic Hras128 rats. These results suggest that Na-AsA is a pure promoter but not a complete carcinogen in rats.

Key Words: Urinary bladder carcinogenesis • sodium L-ascorbate • human c-Ha-ras proto-oncogene transgenic rats • transitional cell carcinoma • in vivo carcinogenicity bioassay • human cancer risk assessment

Abbreviations: Na-AsA, Sodium ascorbate • BBN, N-butyl-N-(4-hydroxybutyl)nitrosamine • TCC, transitional cell carcinoma


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