STIMULATION OF PEROXISOMAL PALMITOYL-COA OXIDASE ACTIVITY BY CIPROFIBRATE IN HEPATIC CELL-LINES - COMPARATIVE-STUDIES IN FAO, MH1C1 AND HEPG2 CELLS

The response of two rat cell lines, Fao and MH1C1, and one human cell line, HepG2, to the peroxisome proliferator ciprofibrate, was studied. Using a fluorometric assay for palmitoyl-CoA oxidase, the dose- and t ime-dependent increase of this enzymatic activity was determined. From the lowest concentration (100 muM) stimulation is evident in the two rat cell lines. In the Fao line, the activity was stimulated reaching a seven-fold increase over the control level at 250 muM after 72 h of treatment. In the MH1C1 line, the maximum stimulation, four- to five-f old, was obtained at 250 and 500 muM after 72 h. In the HepG2 cell lin e, activity increased two-fold at 250 muM after 72 h reaching a three- fold increase at 1000 muM after 48 h. Ciprofibrate was more toxic to F ao cells than to MH1C1 and HepG2 cells which is also the order of the acyl-CoA oxidase stimulation by ciprofibrate. These preliminary result s suggest that the two rat cell lines are appropriate for investigatin g the induction of peroxisomal beta-oxidation enzymes and the expressi on of their genes. The HepG2 cell line is a complementary model for th e study of interspecies differences in the response to peroxisomal pro liferators and of the peroxisomal functions implied in the lipid metab olism of human liver.