Lack of urinary bladder carcinogenicity of sodium L-ascorbate in human c-Ha-ras proto-oncogene transgenic rats

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...

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Published inToxicologic pathology Vol. 33; no. 7; p. 764
Main Authors Morimura, Keiichirou, Kang, Jin Seok, Wei, Min, Wanibuchi, Hideki, Tsuda, Hiroyuki, Fukushima, Shoji
Format Journal Article
LanguageEnglish
Published United States 01.01.2005
Subjects
Animals
Animals, Genetically Modified
Ascorbic Acid - toxicity
Carcinogenicity Tests
Genes, ras - genetics
Rats
Survival Analysis
Urinary Bladder - pathology
Urinary Bladder Neoplasms - chemically induced
Urinary Bladder Neoplasms - genetics
Urinary Bladder Neoplasms - pathology
Vitamins - toxicity
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Summary: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.
ISSN:0192-6233
DOI:10.1080/01926230500416336