Use of a combined human liver microsome-estrogen receptor binding assay toassess potential estrogen modulating activity of PCB metabolites

Polychlorinated biphenyls (PCBs) are metabolized by hydroxylation; some of these hydroxylated metabolites exhibit estrogen-like activity in animal mod els. Because PCBs may have effects on human health, it is of interest to de termine if human tissues also metabolize PCBs to potentially estrogenic met abolites. In this study metabolites of seven PCBs with different degrees an d positions of chlorination, generated by human liver microsomal reaction m ixtures (MRM) have been examined, and their affinity for human recombinant estrogen receptor-alpha (ER) has been tested before and after HPLC fraction ation. Two of the three MRMs with di-chloro-biphenyls (BPs, 2,5BP and 3,4BP ), one of the three MRMs with tetra-BPs (2,6,2',6'BP), and one hexa-BP (2,4 ,6,2',4',6'BP) generated metabolites that competed for ER. HPLC of the ER-b inding MRMs generated fractions that also exhibited ER-binding. This study shows the usefulness of combining in vitro metabolism and an ER-binding ass ay in initial identification of PCBs with estrogen-modulating potential. (C ) 2000 Elsevier Science Ireland Ltd. All rights reserved.