Use of a combined human liver microsome-estrogen receptor binding assay to assess 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 models. Because PCBs may have effects on human health, it is of interest to determine if human tissues also metabolize PCBs to potentially estrogenic metabolites. In this study metabolites of seven PCBs with different degrees and positions of chlorination, generated by human liver microsomal reaction mixtures (MRM) have been examined, and their affinity for human recombinant estrogen receptor-alpha (ER) has been tested before and after HPLC fractionation. 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-binding MRMs generated fractions that also exhibited ER-binding. This study shows the usefulness of combining in vitro metabolism and an ER-binding assay in initial identification of PCBs with estrogen-modulating potential.
Vakharia
D D
DD
New York State Department of Health, Wadsworth Center, Empire State Plaza, P.O. Box 509, Albany, NY 12201-0509, USA.
Gierthy
J F
JF
D000085:Acetates / Q000737:chemistry; D001667:Binding, Competitive / Q000187:drug effects; D001711:Biotransformation; D002474:Cell-Free System / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004958:Estradiol / Q000378:metabolism; D020847:Estrogen Receptor Modulators / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D006801:Humans; D006900:Hydroxylation; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000378:metabolism* / Q000493:pharmacokinetics; D011960:Receptors, Estrogen / Q000378:metabolism*
D000085:Acetates; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D004958:Estradiol; C007650:ethyl acetate; D011078:Polychlorinated Biphenyls