EFFECTS OF PCBS (AROCLOR-1254) ON CYTOCHROME-P450 EXPRESSION AND MONOOXYGENASE ACTIVITIES IN CULTURED FETAL-RAT HEPATOCYTES

Polychlorinated biphenyls (PCBs) are widespread residual micropollutan ts which accumulate in living organisms, probably as a consequence of their high lipophilicity. Cultured foetal rat hepatocytes used as targ et cells constitute an interesting in vitro model for studying the mec hanisms of action of PCBs. In this paper, and the accompanying one (To xicology 98 (1995) 83-94), we have used this model to investigate the effects of PCBs on several cellular parameters, The inducibility of CY PIA1 is the most sensitive parameter studied, as shown by the inductio n of ethoxycoumarin-O-deethylase and ethoxyresorufin-O-deethylase acti vities at PCB concentrations as low as 1 mu M. Dexamethasone treatment of the cells potentiates this induction. PCB induction is reversible and occurs even in cells cultured for several days. CYP2B and CYP3A se em unaffected by PCBs in this experimental system. By inducing CYP1A1, PCBs can trigger the 'activation' of xenobiotics, such as polycyclic hydrocarbons, into mutagenic compounds.