Takizawa Tamotsu, Mitsumori Kunitoshi, Tamura Toru, Nasu Masahiro, Ueda Makoto, Imai Toshio, Hirose Masao
Division of Pathology, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Toxicol Sci. 2003 Jun;73(2):287-93. doi: 10.1093/toxsci/kfg094. Epub 2003 Apr 15.
In order to evaluate the tumorigenic potential of kojic acid (KA), used as a food additive for preventing enzymatic browning of crustaceans and a cosmetic agent for the purpose of skin whitening, heterozygous p53-deficient CBA [p53(+/-)] mice, which are recognized as useful for detecting genotoxic carcinogens, and wild-type littermates [p53(+/+) mice] were fed diet containing 0, 1.5, and 3% KA for 26 weeks. KA induced diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells with decreased serum thyroxine levels in both p53 (+/-) and p53 (+/+) mice, but caused no thyroid tumors. In the liver, the incidence of altered hepatocellular foci was significantly increased at 1.5 and 3% in p 53(+/-) and 1.5% in p53 (+/+) mice, and that of hepatocellular adenomas was increased at 1.5 and 3% in p 53(+/-) and 3% in p53 (+/+) mice. p53 (+/-) mice thus appeared to be more susceptible in terms of the tumorigenic dose of KA with a greater prevalence of hepatic proliferative lesions. The results of the present study indicate tumorigenic potential of KA in the liver, but not thyroid follicular epithelial cells in CBA mice and a contribution of genotoxicity on hepatocellular tumor development cannot be ruled out.
为了评估 kojic acid（KA）的致瘤潜力，KA 被用作防止甲壳类动物酶促褐变的食品添加剂以及用于皮肤美白的化妆品原料，将公认对检测遗传毒性致癌物有用的杂合 p53 缺陷型 CBA [p53(+/-)] 小鼠和野生型同窝仔鼠 [p53(+/+) 小鼠] 喂食含 0%、1.5% 和 3% KA 的饲料 26 周。KA 在 p53(+/-) 和 p53(+/+) 小鼠中均诱导甲状腺滤泡上皮细胞弥漫性肥大和增生，同时血清甲状腺素水平降低，但未引起甲状腺肿瘤。在肝脏中，p53(+/-) 小鼠中 1.5% 和 3% 以及 p53(+/+) 小鼠中 1.5% 的情况下，肝细胞灶性改变的发生率显著增加，p53(+/-) 小鼠中 1.5% 和 3% 以及 p53(+/+) 小鼠中 3% 的情况下，肝细胞腺瘤的发生率增加。因此，就 KA 的致瘤剂量而言，p53(+/-) 小鼠似乎更易感性，肝增殖性病变的发生率更高。本研究结果表明 KA 在 CBA 小鼠肝脏中具有致瘤潜力，但在甲状腺滤泡上皮细胞中没有，并且不能排除遗传毒性对肝细胞肿瘤发生的作用。
