Characterization of Genotoxicity of Kojic Acid by Mutagenicity in Salmonella and Micronucleus Induction in Rodent Liver
Open Access
- 1 January 2006
- journal article
- Published by Japanese Environmental Mutagen Society in Genes and Environment
- Vol. 28 (1), 31-37
- https://doi.org/10.3123/jemsge.28.31
Abstract
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.Keywords
This publication has 14 references indexed in Scilit:
- Evaluation of liver and peripheral blood micronucleus assays with 9 chemicals using young ratsMutation Research/Genetic Toxicology and Environmental Mutagenesis, 2005
- An assessment of the genotoxicity and human health risk of topical use of kojic acid [5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one]Food and Chemical Toxicology, 2003
- Changes in thyroid function during development of thyroid hyperplasia induced by kojic acid in F344 ratsCarcinogenesis: Integrative Cancer Research, 1999
- An Analysis of the Linearized Equations for Axisymmetric Deformations of Hyperelastic CylindersMathematics and Mechanics of Solids, 1999
- Promoting effects of kojic acid due to serum TSH elevation resulting from reduced serum thyroid hormone levels on development of thyroid proliferative lesions in rats initiated with N-bis(2-hydroxypropyl)nitrosamineCarcinogenesis: Integrative Cancer Research, 1999
- Induction of Thyroid Tumours in(C57BL/6N×C3H/N)F1 Mice by Oral Administration of Kojic AcidFood and Chemical Toxicology, 1998
- Revised methods for the Salmonella mutagenicity testMutation Research/Environmental Mutagenesis and Related Subjects, 1983
- Mutagenicity and dominant lethal test of kojic acid. Ames test, forward mutation test in cultured chinese hamster cells and dominant lethal test in mice.The Journal of Toxicological Sciences, 1982
- Mutagenicity of 1,2-dicarbonyl compounds: Maltol, kojic acid, diacetyl and related substancesMutation Research/Genetic Toxicology, 1979
- Mutagenicities of N-nitrosamines on salmonellaMutation research. Reviews in mutation research, 1977