Hepatocellular tumor induction in heterozygous p53-deficient CBA mice by a 26-week dietary administration of kojic acid.
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.
Takizawa
Tamotsu
T
Division of Pathology, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Mitsumori
Kunitoshi
K
Tamura
Toru
T
Nasu
Masahiro
M
Ueda
Makoto
M
Imai
Toshio
T
Hirose
Masao
M
D018248:Adenoma, Liver Cell / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D020518:Focal Nodular Hyperplasia / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009183:Mycotoxins / Q000008:administration & dosage / Q000633:toxicity*; D011753:Pyrones / Q000008:administration & dosage / Q000633:toxicity*; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics
D002273:Carcinogens; D009183:Mycotoxins; D011753:Pyrones; D016159:Tumor Suppressor Protein p53; C011890:kojic acid