PHENOTYPIC ALTERATION OF HEPATOCELLULAR FOCI IN RATS TREATED WITH CLOFIBRATE AND PHENOBARBITAL

In male F344 rats pretreated with diethylnitrosamine (DEN), subsequent administration of clofibrate increased the proportion of eosinophilic foci, to become the most abundant type, and reduced numbers of basoph ilic, clear and vacuolated foci, the total not being changed. A simila r shift towards eosinophilia was also observed in phenobarbital-treate d animals, but in this case clear increases in total number and area w ere apparent. Expression of the glutathione S-transferase placental fo rm (GST-P) in foci was much lowered by clofibrate treatment, while the proportion of positive foci was very high in both phenobarbital and c ontrol groups. A marked contrast was found with eosinophilic foci, wit h 74% positive after phenobarbital as compared to only 15% for clofibr ate. Thus, the decrease in GST-P positive foci by clofibrate was mainl y due to increased negativity in the most abundant eosinophilic type f oci. In a long-term feeding study without DEN initiation, similar nega tivity of foci was observed and, furthermore, only minimal effects of clofibrate on foci development was revealed in both young and old anim als.