Human (HepG2) and rat (MH1C1)
hepatoblastoma cells were incubated with different concentrations of the hypolipidaemics
cetaben,
clofibrate and
thyroxine. The enzymatic activities of
catalase,
peroxisomal bifunctional enzyme,
succinate dehydrogenase, and 3-oxoacyl-CoA thiolase were measured. In order to determine the point of regulation of the enzymatic activities Northern and Slot blot experiments with probes for
peroxisomal 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 (up to 119% of control) was less pronounced. In MH1C1 cells
catalase activity was not changed by any of the drugs. The activity of the
peroxisomal bifunctional enzyme was not affected in HepG2 cells by
clofibric acid and
cetaben, whereas the
mRNA level was elevated to 2.3 fold by 10 micromol/l
cetaben. At high concentrations of
cetaben all
enzyme activities 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 rat, but the results from the human and rat
hepatoblastoma cells correlate with the findings in whole man and rat, so that a human in vitro system 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
enzyme system.