Effects of PCBs (Aroclor 1254) on cytochrome-P450 expression and monooxygenase activities in cultured foetal rat hepatocytes.
Polychlorinated biphenyls (PCBs) are widespread residual micropollutants which accumulate in living organisms, probably as a consequence of their high lipophilicity. Cultured foetal rat hepatocytes used as target cells constitute an interesting in vitro model for studying the mechanisms of action of PCBs. In this paper, and the accompanying one (Toxicology 98 (1995) 83-94), we have used this model to investigate the effects of PCBs on several cellular parameters. The inducibility of CYPIA1 is the most sensitive parameter studied, as shown by the induction of ethoxycoumarin-O-deethylase and ethoxyresorufin-O-deethylase activities at PCB concentrations as low as 1 microM. Dexamethasone treatment of the cells potentiates this induction. PCB induction is reversible and occurs even in cells cultured for several days. CYP2B and CYP3A seem unaffected by PCBs in this experimental system. By inducing CYP1A1, PCBs can trigger the 'activation' of xenobiotics, such as polycyclic hydrocarbons, into mutagenic compounds.
Roelandt
L
L
Université de Liege, Laboratoire de Chimie Médicale, Sart Tilman, Belgium.
Todaro
A
A
Thomé
J P
JP
Kremers
P
P
D015660:7-Alkoxycoumarin O-Dealkylase / Q000187:drug effects; D000818:Animals; D001140:Aroclors / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D020111:Chlorodiphenyl (54% Chlorine); D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005333:Fetus / Q000166:cytology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008954:Models, Biological; D010088:Oxidoreductases / Q000187:drug effects; D010105:Oxygenases / Q000187:drug effects*; D051381:Rats; D013997:Time Factors
D001140:Aroclors; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D019363:Cytochrome P-450 CYP1A1