INDUCTION OF THYROID-TUMORS IN (C57BL 6NXC3H/N)F-1 MICE BY ORAL-ADMINISTRATION OF KOJIC ACID/

The tumorigenicity of kojic acid (KA), which is widely used for food a nd cosmetics in Japan, was examined in B6C3F(1) mice. Female and male animals were divided into three groups and given 0, 1.5 and 3.0% KA co ntaining food from the age of 6 weeks. Al sacrifice after 20 months, t hyroid weights were significantly increased in both sexes of mice rece iving KA, especially in the male groups. The enlarged thyroid glands h istologically featured diffuse hyperplasia and follicular adenomas, th e incidences of the latter being 65% and 87%, respectively in 1.5% and 3.0% KA-treated males, significantly higher than the control value of 2%. In the females, the figures were 2%, 8% and 80% in the 0%, 1.5% a nd 3.0% KA groups, respectively. The serum free T-3 levels in the 3.0% KA animals of both sexes at month 6 were significantly lower than in the controls. On the other hand, their serum TSH levels were higher, a lthough the differences disappeared at later time points. In conclusio n, continuous administration of high dose of KA induces thyroid adenom as in male and female B6C3F(1) mice, presumably by a mechanism involvi ng decrease in serum free T-3 levels and increased TSH. (C) 1998 Elsev ier Science Ltd. All rights reserved