Structure dependent induction of CYP1A by polychlorinated biphenyls in hepatocytes of male castrated pigs

Hepatocytes cultures prepared from castrated pig hepatocytes (Great Yorkshi re x Dutch Landrace), as a model for human liver, were used to study the ef fect of twenty polychlorinated biphenyls (PCBs) on CYP1A activity, measured as the dealkylation of either ethoxyresorufin or methoxyresorufin. The sel ection; of the PCBs was based on their differences in physico-chemical prop erties. The non-ortho and mono-ortho substituted PCBs were the most potent CYP1A inducers in pig hepatocytes. In addition, several multiple-ortho subs tituted congeners, with five or more chlorine atoms, were inducers of CYP1A activity as well. Their relative effect potencies (REP) were proximately 1 0,000 times lower than the most potent congener, 3,3',4,4',5 PeCB (PCB#126) . Using partial least-squares (PLS) modeling, predictions of CYP1A activity could be made fur all tetra to hepta substituted congeners. Several multip le-ortho substituted PCBs, which are highly abundant in the biotic and abio tic environment, have been found to induce CYP1A activity in pig hepatocyte s. Because induction of CYP1A activity is used as biomarker for Air-recepto r mediated responses, it is suggested to include these congeners in future risk assessment. (C) 2000 Elsevier Science Ltd. All rights reserved.