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 activity and the aneugenic properties of griseofulvin. The present study was conducted to explore this relationship. Griseofulvin was evaluated both for its potential promoting activity in liver carcinogenesis in partially hepatectomized F344 male rats initiated by diethylnitrosamine and for its genotoxic potential in the peripheral blood micronucleus assay. Rats were treated daily with 2,000 mg/kg body weight by oral gavage for 12 weeks in the medium-term carcinogenesis bioassay. GST-P-positive foci (mean number and surface area) and altered cell foci were compared in the liver of rats treated with griseofulvin alone, diethylnitrosamine alone,and griseofulvin in addition to diethylnitrosamine by using immunohistochemical and histopathological evaluation, respectively. This evaluation allowed the conclusion that griseofulvin did not initiate the carcinogenic process but rather had a potential in the liver for tumor promoting activity. Griseofulvin was found to be negative in the rat peripheral blood micronucleus test when given at a daily oral dose of 2,000 mg/kg body weight for at least 3 weeks.
Labay
K
K
Agence Française de Sécurité Sanitaire des Aliments, Laboratoire d'Etudes et de Recherches sur les Médicaments Vétérinaires et les Désinfectants, Fougéres Cedex, France. k.labay@fougeres.afssa.fr
Ould-Elhkim
M
M
Klés
V
V
Guffroy
M
M
Poul
J M
JM
Sanders
P
P
D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity*; D005982:Glutathione Transferase / Q000378:metabolism; D006118:Griseofulvin / Q000633:toxicity*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000935:Antifungal Agents; D006118:Griseofulvin; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase