Induction of Hepatocellular Proliferative Lesions in CBA Mice by a 26-week Dietary Administration of Kojic Acid

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In our previous study in which diets containing 0, 1.5 or 3% Kojic acid (KA) were administered to heterozygous p53-deficient mice of the CBA strain [p53 (+/-) mice] and their wild-type littermates [p53 (+/+) mice] for 26 weeks, the incidences of hepatocellular adenomas as well as altered hepatocellular foci were increased in p53 (+/-) and p53 (+/+) mice of the KA treated groups without initiation, as compared to those in the untreated control mice. In order to confirm the reproducibility of the induction of hepatocellular proliferative lesions in p53 (+/+) mice given KA, male CBA mice were given dietary administration of 0, 0.5, 1 or 2% KA for 26 weeks. Body weight gain in the 2% KA group was depressed after week 20 as compared to the corresponding control group. Significant increases of absolute and relative liver weights were observed in the groups treated with 1% and 2% KA. The incidences of hepatocellular adenomas in the control and 0.5, 1 and 2% KA groups were 5, 17, 10 and 21%, respectively, and those of hepatocellular foci in these groups were 15, 39, 45 and 47%, respectively, the difference between the control and 2% KA groups being statistically significant. The mean values for multiplicity of hepatocellular adenomas in the control and 0.5, 1 and 2% KA groups were 0.05, 0.2, 0.2 and 0.2, respectively, and those for hepatocellular foci were 0.2, 0.6, 0.8 and 0.6, respectively. The results of the present study suggest that KA has a hepatocarcinogenic potential in CBA mice.
日本毒性病理学会の論文
2005-09-30

Induction of Hepatocellular Proliferative Lesions in CBA Mice by a 26-week Dietary Administration of Kojic Acid

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