Biochemical effects of 12-O-tetradecanoylphorbol-13-acetate, retinoic acid, phenobarbital, and 5-azacytidine on a normal rat liver epithelial cell line.
The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), all trans-retinoic acid (RA), 5-azacytidine (5-AC), and phenobarbital (PB) on the activities of seven enzymes and/or isozymes of a diploid rat liver epithelial cell line have been studied. At 0.1 microgram/ml, TPA depressed the specific activities of lactate dehydrogenase and gamma-glutamyl transpeptidase, whereas 2 mM PB depressed gamma-glutamyl transpeptidase and alkaline phosphatase. At 0.01 microgram/ml, RA markedly depressed the activity of NADH-diaphorase and lactate dehydrogenase but enhanced the activity of alkaline phosphatase. Only 2 microM 5-AC caused the most significant shift of lactate dehydrogenase isozyme toward the "muscle"-type isozyme. Histochemical studies revealed that PB and 5-AC induced focal areas of cells with glycogen deposits, but no significant changes in either ultrastructure or alpha-fetoprotein and albumin immunohistochemical staining pattern were observed to suggest hepatocytic differentiation. Although none of the enzymatic changes could be consistently correlated with the effects of these biological modifiers on the cellular growth rate, the effect of RA on NADH-diaphorase, lactate dehydrogenase, and alkaline phosphatase activities was the opposite of the changes observed during carcinogenesis of these rat liver epithelial cells by multiple treatments with N-methyl-N'-nitro-N-nitrosoguanidine. The depression of gamma-glutamyl transpeptidase activity by PB is contradictory to that observed histochemically in hepatocytes in vivo, but such discrepancy may be related to the differences in cell type, growth conditions, or duration of exposure.
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
D005353:Fibronectins; D010704:Phorbols; D014212:Tretinoin; D001374:Azacitidine; D013755:Tetradecanoylphorbol Acetate; D010634:Phenobarbital