Cetaben-induced changes on the morphology and peroxisomal enzymes in MH1C1rat hepatoma cells and HepG2 human hepatoblastoma cells

Human HepG2 and rat MH1C1 hepatoma cell lines were examined for their respo nse to cetaben, an exceptional type of peroxisome proliferator. Shape chang e and proliferation of peroxisomes as well as induction of selected peroxis omal enzymes catalase, acyl-CoA oxidase, and peroxisomal bifunctional enzym e, were assessed in response to cetaben. in MH1C1 cells, peroxisomes were s een in clusters displaying typical features of microperoxisomes. Cetaben ca used little but reversible proliferation and morphological heterogeneity wi th the occurrence of dumbbell-shaped and cup-shaped peroxisomal profiles. P eroxisomes in HepG2 cells showed marked variation in size and shape. Cetabe n treatment of HepG2 cells caused disintegration of Golgi regions and augme nted mitochondrial matrix. Interestingly, MH1C1 cells showed different subu nit composition of acyl-CoA oxidase in immunoblot analysis: only subunit A at 72 kDa was detected but not the cleavage products. In situ hybridization underlined the marked morphological heterogeneity observed, and both cell lines revealed different stages of gene expression. Our results indicate th at cetaben represents an extraordinary type of peroxisomal proliferator wit h pleiotropic effects on human and rat hepatoma cells, and, at least in the human hepatoma cell line HepG2, these effects are not restricted to peroxi some proliferation.