ToxSci Advance Access originally published online on April 15, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Toxicological Sciences 73, 287-293 (2003)
Copyright © 2003 by the Society of Toxicology
CARCINOGENICITY |
Hepatocellular Tumor Induction in Heterozygous p53-Deficient CBA Mice by a 26-Week Dietary Administration of Kojic Acid
* Division of Pathology, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan;
Department of Molecular and Environmental Pathology, School of Medicine, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan;
Laboratory of Veterinary Pathology, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8, Saiwai-cho, Fuchu, Tokyo 183-8509, Japan; and
Panapharm Laboratories Co., Ltd., 1285, Kurisaki-machi, Uto, Kumamoto 869-0425, Japan
In order to evaluate the tumorigenic potential of kojic acid (KA), used as a food additive for preventing enzymatic browning of crustaceans and a cosmetic agent for the purpose of skin whitening, heterozygous p53-deficient CBA [p53(+/-)] mice, which are recognized as useful for detecting genotoxic carcinogens, and wild-type littermates [p53(+/+) mice] were fed diet containing 0, 1.5, and 3% KA for 26 weeks. KA induced diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells with decreased serum thyroxine levels in both p53 (+/-) and p53 (+/+) mice, but caused no thyroid tumors. In the liver, the incidence of altered hepatocellular foci was significantly increased at 1.5 and 3% in p 53(+/-) and 1.5% in p53 (+/+) mice, and that of hepatocellular adenomas was increased at 1.5 and 3% in p 53(+/-) and 3% in p53 (+/+) mice. p53 (+/-) mice thus appeared to be more susceptible in terms of the tumorigenic dose of KA with a greater prevalence of hepatic proliferative lesions. The results of the present study indicate tumorigenic potential of KA in the liver, but not thyroid follicular epithelial cells in CBA mice and a contribution of genotoxicity on hepatocellular tumor development cannot be ruled out.
Key Words: kojic acid; hepatocarcinogenesis; heterozygous p53-deficient mice.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Takizawa, T. Imai, J.-i. Onose, M. Ueda, T. Tamura, K. Mitsumori, K. Izumi, and M. Hirose Enhancement of Hepatocarcinogenesis by Kojic Acid in Rat Two-Stage Models after Initiation with N-bis(2-hydroxypropyl)nitrosamine or N-diethylnitrosamine Toxicol. Sci., September 1, 2004; 81(1): 43 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tani, R. R. Maronpot, J. F. Foley, J. K. Haseman, N. J. Walker, and A. Nyska Follicular Epithelial Cell Hypertrophy Induced by Chronic Oral Administration of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Female Harlan Sprague--Dawley Rats Toxicol Pathol, January 1, 2004; 32(1): 41 - 49. [Abstract] [PDF]
|
|