Lack of urinary bladder carcinogenicity of sodium L-ascorbate in human c-Ha-ras proto-oncogene Transgenic rats
Lack of urinary bladder carcinogenicity of sodium L-ascorbate in human c-Ha-ras proto-oncogene Transgenic rats
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DOI：
10.1080/01926230500416336
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发表时间：
2005-01-01
影响因子：
1.5
通讯作者：
Fukushima，S
中科院分区：
文献类型：
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作者：
Morimura，K;Kang，JS;Fukushima，S
L-抗坏血酸钠（Na-AsA）被广泛认为是大鼠膀胱癌发生的肿瘤促进剂，但在标准的2年生物测定中测试为阴性。在本研究中，膀胱癌易感的转基因大鼠命名为Hras 128，以进一步检查的Na-AsA的致瘤性。将40只7周龄雄性转基因（Tg）大鼠和42只同窝非转基因（Non-tg）大鼠分为4组，分别给予含或不含5% Na-AsA的MF粉饲料57周。Tg大鼠表现出显着较短的生存期相比，非tg，独立的钠-抗坏血酸治疗。用Na-AsA处理的Tg大鼠显示出与未用Na-AsA处理的那些大鼠（15.4%）相比的略高的癌发生率（29.6%），但这没有统计学意义。此外，包括乳头状瘤在内的膀胱肿瘤总发病率无统计学差异（使用Na-AsA，37.0%;不使用Na-AsA，30.8%）。在非tg大鼠中未检测到膀胱肿瘤。在用或不用Na-AsA治疗的Tg大鼠中注意到各种器官中的各种其他病变，但组间差异不明显。总之，Na-AsA在高膀胱癌易感性转基因Hras 128大鼠中未显示致瘤性。这些结果表明，Na-AsA是一个纯粹的启动子，但不是一个完整的致癌物在大鼠。
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.