DIFFERENTIAL INDUCTION OF PEROXISOMAL ENZYMES BY HYPOLIPIDAEMICS IN HUMAN (HEPG2) AND RAT (MH1C1) HEPATOMA-CELL LINES

Human (HepG2) and rat (MH1C1) hepatoblastoma cells were incubated with different concentrations of the hypolipidaemics cetaben, clofibrate a nd thyroxine. The enzymatic activities of catalase, peroxisomal bifunc tional enzyme, succinate dehydrogenase, and 3-oxoacyl-CoA thiolase wer e measured. In order to determine the point of regulation of the enzym atic activities Northern and Slot blot experiments with probes for per oxisomal bifunctional enzyme, catalase and fatty acyl CoA oxidase were performed on total RNA. Catalase activity was enhanced in HepG2 cells treated with 3 mmol/l clofibric acid to 135% of control and the mRNA value to 2.6 fold, whereas in cetaben treated cells the enhancement (u p to 119% of control) was less pronounced. In MH1C1 cells catalase act ivity was not changed by any of the drugs. The activity of the peroxis omal bifunctional enzyme was not affected in HepG2 cells by clofibric acid and cetaben, whereas the mRNA level was elevated to 2.3 fold by 1 0 mu mol/l cetaben. At high concentrations of cetaben all enzyme activ ities were decreased in both cell lines due to its high cytotoxicity. Our data show that, due to the differences in the genomic organisation , the regulation of the enzyme activities is different in human and ra t, but the results from the human and rat hepatoblastoma cells correla te with the findings in whole man and rat, so that a human in vitro sy stem is more suitable for pharmacological tests. These results suggest that the human hepatoma cell line HepG2 may be a useful model system for studies of the influence of hypolipidaemics on the peroxisomal enz yme system.