Lack of modification of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-induced hepatocarcinogenesis in rats by fenbendazole--a CYP1A2 inducer

Abstract

Fenbendazole (FBZ) is an anthelmintic drug known to be a potent CYP1A2 inducer. Combined effects of FBZ on 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-induced hepatocarcinogenesis in rats were investigated using a medium-term liver bioassay system. No modifying influence was found in terms of glutathione S-transferase placental-form positive foci development although CYP1A2 protein expression in the livers of rats that were given MeIQx and FBZ was 2.3-fold higher than with MeIQx alone. NAT2 mRNA expression did not differ among the groups as revealed by quantitative reverse transcriptase-polymerase chain reaction analysis. These results suggest that elevated CYP1A2 expression is not sufficient to enhance MeIQx-induced hepatocarcinogenesis.