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In vivo Genotoxic Potential of Kojic Acid in Rodent Multiple Organs Detected by the Comet Assay

机译：彗星试验检测出曲酸在啮齿类动物多器官中的体内遗传毒性潜力

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Kojic acid has been used for skin whitening as a cosmetic agent. Kojic acid is believed to be hepatocarcinogenic in mice. We conducted the comet assay in mouse and rat multiple organs to evaluate its in vivo genotoxic potential.Kojic acid induced dose-dependent DNA damage in ddY mouse stomach and liver and in Wistar rat stomach, liver, lung, and bone marrow after a single gavage administration at ≦1000 mg/kg. Its hepatic genotoxicity detected by the comet assay seems to contradict to absence of its hepatic tumor initiating activity revealed by the two-step carcinogenesis studies with mice and rats. However, considering the possibility that the sensitivity of the two-step carcinogenesis studies performed are not high enough to detect weak initiating activity of a chemical, it would be premature to conclude that its hepatic genotoxicity contradicts to the absence of initiating activity. In mice fed a diet containing 3% kojic acid for up to 10 days, DNA migration increased in the stomach after feeding for 2 days but it did not increased after feeding for 1 day and ≧4 days. In the colon, DNA migration after feeding of 3%kojic acid for 2 days was higher than the control values, but this increase was not statistically signicant. In the stomach and colon, any statistically signicant increases in DNA migration were not observed after feeding of 1.5% kojic acid. In the liver, DNA migration increased with feeding period and the increases after feeding of 3% and 1.5% kojic acid for ≧4 days and 6 days, respectively, were statistically signicant. Our present results suggested good correlation between hepatocarcinogenicity of kojic acid and increasing tendency of its hepatic genotoxicity with dosing period when it is given to mice continuously in the diet.
机译：曲酸已被用作皮肤增白剂作为美容剂。据信曲酸在小鼠中是肝癌的。我们在小鼠和大鼠的多个器官中进行了彗星试验，以评估其体内遗传毒性的潜力。一次强饲法后，曲霉酸对ddY小鼠胃和肝脏以及Wistar大鼠胃，肝，肺和骨髓中的剂量依赖性DNA损伤以≤1000mg/ kg的剂量施用。通过彗星试验检测到的其肝遗传毒性似乎与小鼠和大鼠的两步致癌研究所揭示的肝肿瘤起始活性的缺乏相矛盾。但是，考虑到进行的两步致癌研究的敏感性不够高，不足以检测到化学药品的弱启动活性，现在断定其肝脏遗传毒性与缺乏启动活性相矛盾尚为时过早。在喂食含3％曲酸的饮食长达10天的小鼠中，喂食2天后胃中的DNA迁移增加，但喂食1天和≥4天后DNA迁移没有增加。在结肠中，饲喂3％曲酸2天后的DNA迁移高于对照值，但这种增加在统计学上没有显着意义。在胃和结肠中，饲喂1.5％曲酸后未观察到DNA迁移的任何统计学显着增加。在肝脏中，DNA迁移随进食时间增加而增加，分别进食3％和1.5％曲酸≥4天和6天后，DNA迁移具有统计学意义。我们目前的研究结果表明，在饮食中连续给予小鼠曲酸，其肝致癌性与给药剂量期间肝遗传毒性的增加趋势之间具有良好的相关性。

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