Characterization of Genotoxicity of Kojic Acid by Mutagenicity in Salmonella and Micronucleus Induction in Rodent Liver
Characterization of Genotoxicity of Kojic Acid by Mutagenicity in Salmonella and Micronucleus Induction in Rodent Liver
复制标题
曲酸对沙门氏菌的致突变性和啮齿动物肝脏微核诱导的遗传毒性特征
DOI：
10.3123/jemsge.28.31
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发表时间：
2006
影响因子：
1.7
通讯作者：
M. Nagao
中科院分区：
文献类型：
--
作者：
S. Ishikawa;Y. Sasaki;Satomi Kawaguchi;M. Mochizuki;M. Nagao
生产用作试剂、食品添加剂和化妆品的三批曲酸 (KA) 在含有或不含 S9 混合物的鼠伤寒沙门氏菌 TA100 中显示出诱变性，比活性为每毫克 KA 约 100 个回复突变体。由于关于 KA 遗传毒性的报道相互矛盾，我们使用 HPLC 检查了鼠伤寒沙门氏菌的致突变性是由于 KA 本身还是由于 KA 样品中存在的污染物。尽管通过 HPLC 分离了两个 UV 吸收级分，但仅在主要级分中检测到致突变性，且 KA 的特异性致突变活性在 HPLC 分离前后没有变化。通过NMR确认HPLC上主峰级分中的物质为KA。由此证明KA本身具有致突变性，三批样品中均未检测到致突变污染物。由于已知 KA 会在小鼠体内产生肝脏肿瘤，因此我们进一步研究了 KA 在啮齿动物肝脏中的遗传毒性。 KA通过胃插管以每公斤体重1克诱导成年小鼠再生肝脏中的微核（MN）。然而，在未进行部分肝切除的年轻小鼠（3 周龄）中没有诱导出 MN。由于最近在两步致癌性研究中发现KA在小鼠肝脏中没有肿瘤引发活性，因此没有证据表明在小鼠肝脏中检测到的遗传毒性与肝癌发生有关。
Three lots of kojic acid (KA) which were produced for use as a reagent, food additive and in cosmetics were shown to be mutagenic in S. typhimurium TA100 with or without S9 mix, with a specific activity of around 100 revertants per mg of KA. Since there are contradictory reports on genotoxicity of KA, we examined, using HPLC, whether the mutagenicity to S. typhimurium is due to KA itself, or due to contaminants present in the KA samples. Although two UV absorbing fractions were separated by HPLC, mutagenicity was detected only in the major fraction and the specific mutagenic activity of KA did not change before and after HPLC separation. The material in the major peak fractions on HPLC was confirmed to be KA by NMR. Thus it was demonstrated that KA itself is mutagenic and no mutagenic contaminants were detected in the three lots of samples. Since KA is known to produce liver tumors in mice, we further examined the genotoxicity of KA in the liver of rodents. KA induced micronuclei (MN) in the regenerating liver of adult mice by its gastric intubation at 1 g per kg body weight. However, no MN were induced in young mice (3 weeks old) without partial hepatectomy. Since it was recently found that KA had no tumor-initiating activity in the liver of mice in a two-step carcinogenicity study, there is no evidence that the genotoxicity detected in the mouse liver is involved in liver carcinogenesis.