title: Bis(hydroxyphenyl)methane-bisphenol F-metabolism by the HepG2 human hepatoma cell line and cryopreserved human hepatocytes.
abstract: Bisphenol F (BPF) is present in the environment and as a contaminant of food. Humans may, therefore, be exposed to BPF, and an assessment of this risk is required. BPF has been shown to have genotoxic and endocrine-disruptor properties in a human hepatoma cell line (HepG2), which is a model system for studies of xenobiotic toxicity. In this study, we investigated the ability of HepG2 cells to biotransform BPF, because metabolism may affect the observed effects of BPF, and we compared this metabolic capacity with that of human hepatocytes. Cells were incubated for 24 hours with [(3)H]-BPF. The culture medium was then concentrated and its metabolites were isolated by high-performance liquid chromatography and identified by mass spectrometry. BPF was largely metabolized into the corresponding sulfate by the HepG2 cell line. BPF was metabolized into both sulfate and glucuronide by human hepatocytes, but with differences between individuals. The metabolism of BPF in both HepG2 cells and human hepatocytes suggests the existence of a detoxification pathway. Thus, these two cell models differ in metabolic capacity. It is, therefore, very important, when assessing the toxic effects of substances in vitro, to determine, in parallel, the biotransformation capacities of the model used to extrapolate in vivo.
authors.affiliation: Laboratoire de Toxicologie Alimentaire UMR INRA/Université, de Bourgogne/ENESAD 1324, AgroSup Dijon, Dijon, France. coralie.dumont@u-bourgogne.fr
authors.forename: Coralie
authors.initials: C
authors.lastname: Dumont
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Perdu
authors.forename: Georges
authors.initials: G
authors.lastname: de Sousa
authors.forename: Laurent
authors.initials: L
authors.lastname: Debrauwer
authors.forename: Roger
authors.initials: R
authors.lastname: Rahmani
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cravedi
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Chagnon
mesh_terms: D001559:Benzhydryl Compounds / Q000378:metabolism*; D001711:Biotransformation; D018929:Cell Culture Techniques; D002851:Chromatography, High Pressure Liquid; D015925:Cryopreservation; D004785:Environmental Pollutants / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000235:genetics; D013058:Mass Spectrometry; D015394:Molecular Structure; D010957:Plasmids; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics; D000098833:Bisphenol F Compounds
chemical_list: D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; D008156:Luciferases; D001616:beta-Galactosidase; C506487:ESR1 protein, human; C008745:4,4'-bisphenol F; D000098833:Bisphenol F Compounds