Cetaben-induced changes on the morphology and peroxisomal enzymes in MH1C1 rat hepatoma cells and HepG2 human hepatoblastoma cells.
Human HepG2 and rat MH1C1 hepatoma cell lines were examined for their response to cetaben, an exceptional type of peroxisome proliferator. Shape change and proliferation of peroxisomes as well as induction of selected peroxisomal enzymes catalase, acyl-CoA oxidase, and peroxisomal bifunctional enzyme, were assessed in response to cetaben. In MH1C1 cells, peroxisomes were seen in clusters displaying typical features of microperoxisomes. Cetaben caused little but reversible proliferation and morphological heterogeneity with the occurrence of dumbbell-shaped and cup-shaped peroxisomal profiles. Peroxisomes in HepG2 cells showed marked variation in size and shape. Cetaben treatment of HepG2 cells caused disintegration of Golgi regions and augmented mitochondrial matrix. Interestingly, MH1C1 cells showed different subunit 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 that cetaben represents an extraordinary type of peroxisomal proliferator with pleiotropic effects on human and rat hepatoma cells, and, at least in the human hepatoma cell line HepG2, these effects are not restricted to peroxisome proliferation.
Kovacs
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Institute of Medical Chemistry, University of Vienna, Währingerstrasse 10, 1090 Vienna, Austria herbert.stangl@univie.ac.at
Walter
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Stangl
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D010129:4-Aminobenzoic Acid / Q000494:pharmacology*; D042962:Acyl-CoA Oxidase; D000818:Animals; D006528:Carcinoma, Hepatocellular; D002374:Catalase / Q000235:genetics; D015870:Gene Expression; D018197:Hepatoblastoma; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D015151:Immunoblotting / Q000379:methods; D010088:Oxidoreductases / Q000235:genetics; D020675:Peroxisomes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013194:Staining and Labeling; D014407:Tumor Cells, Cultured; D062366:para-Aminobenzoates
D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D062366:para-Aminobenzoates; C018246:cetaben; D010088:Oxidoreductases; D002374:Catalase; D042962:Acyl-CoA Oxidase; D010129:4-Aminobenzoic Acid