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 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.
Morimura
Keiichirou
K
Department of Pathology, Osaka City University Medical School, Osaka, Japan.
Kang
Jin Seok
JS
Wei
Min
M
Wanibuchi
Hideki
H
Tsuda
Hiroyuki
H
Fukushima
Shoji
S
D000818:Animals; D030801:Animals, Genetically Modified; D001205:Ascorbic Acid / Q000633:toxicity*; D015197:Carcinogenicity Tests; D011905:Genes, ras / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D051381:Rats; D016019:Survival Analysis; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D014815:Vitamins / Q000633:toxicity*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014815:Vitamins; D001205:Ascorbic Acid