曲酸在 F344 大鼠中的非遗传毒性作用机制和潜在致癌性阈值。

Non-genotoxic mode of action and possible threshold for hepatocarcinogenicity of Kojic acid in F344 rats.

机构信息

Department of Pathology, Osaka City University Medical School, Abeno-ku, Osaka, Japan.

出版信息

Food Chem Toxicol. 2011 Feb;49(2):471-6. doi: 10.1016/j.fct.2010.11.027. Epub 2010 Nov 26.

DOI:10.1016/j.fct.2010.11.027

Abstract

Kojic acid (KA), a naturally occurring compound, is contained in traditional Japanese fermented foods and is used as a food additive, preservative and a dermatological skin-lightening agent. In the present experiment, initiation (experiment 1) and promotion (experiment 2) effects of KA-induced hepatocarcinogenesis were studied by rat medium-term bioassay for carcinogenicity. Male F344 rats were administered a diet containing 0-2% KA. Experiment 1 demonstrated that KA had no effect on induction of liver preneoplastic lesions or glutathione S-transferase placental form (GST-P) positive foci, in either number or area. In experiment 2, 2% KA treatment significantly increased the number and area of GST-P positive foci, but concentrations less than 0.5% did not. Moreover, 2% KA treatment significantly increased 8-OHdG levels and PCNA positive hepatocytes. The results indicated that low concentrations of KA do not have initiation effects on rat hepatocarcinogenesis, while higher concentrations of KA do promote hepatocarcinogenesis in rats. Thus, the results indicate that KA is a non-genotoxic hepatocarcinogen, showing the possible existence of a perfect threshold.

摘要

曲酸（KA）是一种天然存在的化合物，存在于传统的日本发酵食品中，被用作食品添加剂、防腐剂和皮肤科皮肤增亮剂。在本实验中，通过大鼠中期致癌性生物测定研究了 KA 诱导肝癌的起始（实验 1）和促进（实验 2）作用。雄性 F344 大鼠给予含有 0-2%KA 的饮食。实验 1 表明，KA 对肝前瘤病变或谷胱甘肽 S-转移酶胎盘形式（GST-P）阳性焦点的诱导没有影响，无论是数量还是面积。在实验 2 中，2%KA 处理显著增加了 GST-P 阳性焦点的数量和面积，但浓度低于 0.5%则没有。此外，2%KA 处理显著增加了 8-OHdG 水平和 PCNA 阳性肝细胞。结果表明，低浓度的 KA 对大鼠肝癌的起始没有作用，而高浓度的 KA 确实促进了大鼠肝癌的发生。因此，结果表明 KA 是非遗传毒性肝癌致癌物，表明可能存在完美的阈值。