Altered growth control of rat hepatocytes after treatment with 3,4,3',4'-tetrachlorobiphenyl in vivo and in vitro.
Alterations of hepatocyte growth control by inducers of drug-metabolizing enzymes were investigated using 3,4,3',4'-tetrachlorobiphenyl (TCB) as the inducing agent. TCB was chosen as a selective 3-methylcholanthrene-type inducer and liver tumor promoter which probably exerts its biological actions through binding to the aryl hydrocarbon (Ah) receptor. In vivo treatment of rats with TCB (200 mg/kg) markedly stimulated growth of enzyme altered liver foci and [3H]-thymidine incorporation into nuclear DNA. Hepatocyte cultures from TCB-treated rats were more sensitive to exogenous growth factors such as EGF than those from untreated controls. In vitro TCB exposure of hepatocyte cultures also altered hepatocyte growth control in a dose-dependent manner and induced drug-metabolizing enzymes. TCB treatment in vivo enhanced EGF-stimulated autophosphorylation of the EGF receptor in liver plasma membranes. The results suggest that altered growth control is due to a direct effect of TCB on hepatocytes. The proposed model may be useful to elucidate a possible linkage between the functional stress imposed on hepatocytes by sustained overexpression of an adaptive program and modulation of hepatocyte growth control.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000096:biosynthesis; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010105:Oxygenases / Q000096:biosynthesis; D010766:Phosphorylation; D011078:Polychlorinated Biphenyls / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D004815:Epidermal Growth Factor; D011078:Polychlorinated Biphenyls; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D014453:Glucuronosyltransferase; C028451:3,4,3',4'-tetrachlorobiphenyl