title: Novel pathway of metabolic activation of bisphenol A-related compounds for estrogenic activity.
abstract: We previously demonstrated that estrogenic activity of bisphenol A (BPA) in the yeast estrogen screening assay was increased severalfold after incubation with rat liver S9 fraction in the presence of a NADPH-generating system. In this study, we investigated whether eight BPA-related compounds are similarly activated metabolically by rat liver S9 fraction. Three of the analogs exhibited an increase of estrogenic activity after incubation with rat liver S9 fraction but not with microsomal or cytosolic fraction alone. The structures of the metabolites formed were examined by liquid chromatography/mass spectrometry. In addition to oxidized metabolites such as catechols, we found novel dimer-type metabolites. Some of the putative metabolites were chemically synthesized to confirm their structures. The structural requirements for formation of the metabolites, some of which showed more potent estrogenic activity than the parent substrates, were examined. We have uncovered a new pathway of metabolic activation of certain phenolic compounds, such as BPA analogs, to estrogenic dimer-type compounds.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hiro-koshingai, Kure, Hiroshima 737-0112, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Okuda
authors.forename: Tomoko
authors.initials: T
authors.lastname: Fukuuchi
authors.forename: Masufumi
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Yoshihara
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D001711:Biotransformation; D002396:Catechols / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D003600:Cytosol / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008862:Microsomes, Liver / Q000378:metabolism; D010636:Phenols / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015003:Yeasts / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002396:Catechols; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds