title: Modulation of metabolizing enzymes by bisphenol a in human and animal models.
abstract: Xenobiotics, such as contaminants and drugs, can be converted to potentially toxic reactive metabolites by phase 1 oxidizing enzymes. These metabolites are further detoxified by phase 2 conjugating enzymes and eliminated from cells by phase 3 transporters. Moreover, many of these xenobiotics are also able to induce or inhibit these enzymes, potentially modulating their own toxicity or that of other chemicals. The present review is focused on bisphenol A, a synthetic monomer used for many industrial applications and exhibiting xenoestrogen properties. The impact of this contaminant on all major classes of metabolizing enzymes (i.e., cytochromes P450, glutathione-S-transferases, sulfotransferases, UDP-glucuronyltransferases, and transporters) was reviewed, with a highlight on the modulation of cytochromes P450 involved in steroid metabolism. Interestingly, most of the studies reported in this review show that BPA is able to induce or inhibit metabolizing enzymes at high doses but also at doses compatible with human exposure.
authors.affiliation: INSERM, UMR 991, F-35033 Rennes, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Quesnot
authors.forename: Simon
authors.initials: S
authors.lastname: Bucher
authors.forename: Bernard
authors.initials: B
authors.lastname: Fromenty
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Robin
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000737:chemistry / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D023421:Models, Animal; D010636:Phenols / Q000737:chemistry / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D010636:Phenols; D015238:Sulfotransferases; D015262:Xenobiotics; C006780:bisphenol A; D000098826:Bisphenol A Compounds