Effects of griseofulvin in medium-term liver carcinogenesis assay and peripheral blood micronucleus test in rat

Published data have suggested a possible link between the tumor promoting a ctivity and the aneugenic properties of griseofulvin. The present study was conducted to explore this relationship. Griseofulvin was evaluated both fo r its potential promoting activity in liver carcinogenesis in partially hep atectomized F344 male rats initiated by diethyinitrosamine and for its geno toxic potential in the peripheral blood micronucleus assay. Rats were treat ed daily with 2,000 mg/kg body weight by oral gavage for 12 weeks in the me dium-term carcinogenesis bioassay. GST-P-positive foci (mean number and sur face area) and altered cell foci were compared in the liver of rats treated with griseofulvin alone, diethylnitrosamine alone and griseofulvin in addi tion to diethylnitrosamine by using immunohistochemical and histopathologic al evaluation, respectively. This evaluation allowed the conclusion that gr iseofulvin did not initiate the carcinogenic process but rather had a poten tial in the liver for tumor promoting activity. Griseofulvin was found to b e negative in the rat peripheral blood micronucleus test when given at a da ily oral dose of 2,000 mg/kg body weight for at least 3 weeks. Teratogenesi s Carcinog. Mutagen. 21:441-451, 2001. (C) 2001 Wiley-Liss, Inc.