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

Genes and Environment

Gisho Honda¹  Satomi Kawaguchi³  Takanori Nakamura¹  Yu F. Sasaki⁴  Natsue Yokohama² 

[1] Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University;Chemical Quality Evaluation Div., Canon Inc.;Kobuchisawa Research Laboratories, Fuji Biomedix Co., Ltd.;Laboratory of Genotoxicity, Faculty of Chemical and Biological Engineering, Hachinohe National College of Technology

关键词: kojic acid;    hapatocarcinogenicity;    DNA damage;    comet assay;    gavage;    feeding;   

DOI  :  10.3123/jemsge.30.25

学科分类：分子生物学，细胞生物学和基因

来源: Japanese Environmental Mutagen Society / Nihon Kankyo Hen igen Gakkai

【 摘 要 】

References(26)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 significant. In the stomach and colon, any statistically significant 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 significant. 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.

【 授权许可】

Unknown