title: Cell-specific biotransformation of benzophenone-2 and bisphenol-s in zebrafish and human in vitro models used for toxicity and estrogenicity screening.
abstract: Several human and fish bioassays have been designed to characterize the toxicity and the estrogenic activity of chemicals. However, their biotransformation capability (bioactivation/detoxification processes) is rarely reported, although this can influence the estrogenic potency of test compounds. The fate of two estrogenic chemicals, the UV filter benzophenone-2 (BP2) and the bisphenol A substitute bisphenol S (BPS) was deciphered in eight human and zebrafish in vitro cell models, encompassing hepatic and mammary cellular contexts. BP2 and BPS were metabolized into a variety of gluco- and sulfo-conjugated metabolites. Similar patterns of BP2 and BPS biotransformation were observed among zebrafish models (primary hepatocytes, ZFL and ZELH-zfER cell lines). Interestingly, metabolic patterns in zebrafish models and in the human hepatic cell line HepaRG shared many similarities, while biotransformation rates in cell lines widely used for estrogenicity testing (MELN and T47D-KBLuc) were quantitatively low and qualitatively different. This study provides new data on the comparative metabolism of BP2 and BPS in human and fish cellular models that will help characterize their metabolic capabilities, and underlines the relevance of using in vitro zebrafish-based bioassays when screening for endocrine disrupting chemicals.
authors: †Institut National de l'Environnement Industriel et des Risques (INERIS), Unité Écotoxicologie in vitro et in vivo, F-60550 Verneuil-en-Halatte, France.|‡INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, F-31027 Toulouse, France.|§Toulouse University, INP, UMR 1331 TOXALIM, F-31000 Toulouse, France.
authors: Vincent
authors: V
authors: Le Fol
authors: †Institut National de l'Environnement Industriel et des Risques (INERIS), Unité Écotoxicologie in vitro et in vivo, F-60550 Verneuil-en-Halatte, France.
authors: Selim
authors: S
authors: Aït-Aïssa
authors: ‡INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, F-31027 Toulouse, France.|§Toulouse University, INP, UMR 1331 TOXALIM, F-31000 Toulouse, France.
authors: Nicolas
authors: N
authors: Cabaton
authors: ‡INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, F-31027 Toulouse, France.|§Toulouse University, INP, UMR 1331 TOXALIM, F-31000 Toulouse, France.
authors: Laurence
authors: L
authors: Dolo
authors: ∥IRCM, INSERM U1194, Université Montpellier, ICM, F-34298 Montpellier, France.
authors: Marina
authors: M
authors: Grimaldi
authors: ∥IRCM, INSERM U1194, Université Montpellier, ICM, F-34298 Montpellier, France.
authors: Patrick
authors: P
authors: Balaguer
authors: ‡INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, F-31027 Toulouse, France.|§Toulouse University, INP, UMR 1331 TOXALIM, F-31000 Toulouse, France.
authors: Elisabeth
authors: E
authors: Perdu
authors: ‡INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, F-31027 Toulouse, France.|§Toulouse University, INP, UMR 1331 TOXALIM, F-31000 Toulouse, France.
authors: Laurent
authors: L
authors: Debrauwer
authors: †Institut National de l'Environnement Industriel et des Risques (INERIS), Unité Écotoxicologie in vitro et in vivo, F-60550 Verneuil-en-Halatte, France.
authors: François
authors: F
authors: Brion
authors: ‡INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, F-31027 Toulouse, France.|§Toulouse University, INP, UMR 1331 TOXALIM, F-31000 Toulouse, France.
authors: Daniel
authors: D
authors: Zalko
mesh_terms: D000818:Animals; D001577:Benzophenones / Q000378:metabolism*; D001711:Biotransformation / Q000187:drug effects; D002417:Cattle; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004967:Estrogens / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D010636:Phenols / Q000378:metabolism*; D013450:Sulfones / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism*; D000098831:Bisphenol S Compounds
chemical_list: D001577:Benzophenones; D004967:Estrogens; D010636:Phenols; D013450:Sulfones; C543008:bisphenol S; D000098831:Bisphenol S Compounds; C035476:2,2',4,4'-tetrahydroxybenzophenone