caa a22 4500 445854065 CHVBK 20180317145423.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s00204-011-0721-2 doi (NATIONALLICENCE)springer-10.1007/s00204-011-0721-2 Use of the γH2AX assay for assessing the genotoxicity of bisphenol A and bisphenol F in human cell lines [Elektronische Daten] [Marc Audebert, L. Dolo, E. Perdu, J. Cravedi, D. Zalko] Bisphenol A (BPA) and bisphenol F (BPF) are widely used to manufacture plastics and epoxy resins. Both compounds have been shown to be present in the environment and are food contaminants, with, as a result, a low but chronic exposure of humans. However, the fate and possible bioactivation of these compounds at the level of human cell lines was not completely elucidated yet. In this study, we investigated the ability of human cells (intestinal cell line: LS174T, hepatoma cell line: HepG2, and renal cell line: ACHN) to biotransform BPA and BPF, and focused on the cytotoxicity and genotoxicity of these two bisphenols, through the use of a novel and efficient genotoxic assay based on the detection of histone H2AX phosphorylation. BPA and BPF were extensively metabolized in HepG2 and LS174T cell lines, with stronger biotransformation capabilities in intestinal cells than observed in liver cells. Both cell lines produced the glucuronide as well as the sulfate conjugates of BPA. Conversely, the ACHN cell line was found to be devoid of any metabolic capabilities for the two examined bisphenols. Cytotoxicity was tested for BPA, BPF, as well as one metabolite of BPF produced in vivo in rat, namely dihydroxybenzophenone (DHB). In the three cell lines used, we observed similar ranges of toxicity, with DHB being weakly cytotoxic, BPF exhibiting an intermediary cytotoxicity, and BPA being the most cytotoxic compound tested. BPA and DHB were not found to be genotoxic, whatever the cell line examined. BPF was clearly genotoxic in HepG2 cells. These results demonstrate that some human cell lines extensively metabolize bisphenols and establish the genotoxic potential of bisphenol F. Springer-Verlag, 2011 Bisphenol A nationallicence Bisphenol F nationallicence Metabolism nationallicence Genotoxicity nationallicence H2AX nationallicence LS174T nationallicence Audebert Marc INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, 180 chemin de Tournefeuille, BP 93173, 31027, Toulouse Cedex 3, France aut Dolo L. INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, 180 chemin de Tournefeuille, BP 93173, 31027, Toulouse Cedex 3, France aut Perdu E. INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, 180 chemin de Tournefeuille, BP 93173, 31027, Toulouse Cedex 3, France aut Cravedi J. INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, 180 chemin de Tournefeuille, BP 93173, 31027, Toulouse Cedex 3, France aut Zalko D. INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, 180 chemin de Tournefeuille, BP 93173, 31027, Toulouse Cedex 3, France aut Archives of Toxicology Springer-Verlag 85/11(2011-11-01), 1463-1473 0340-5761 85:11<1463 2011 85 204 https://doi.org/10.1007/s00204-011-0721-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0721-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Audebert Marc INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, 180 chemin de Tournefeuille, BP 93173, 31027, Toulouse Cedex 3, France aut NATIONALLICENCE 700 1- Dolo L. INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, 180 chemin de Tournefeuille, BP 93173, 31027, Toulouse Cedex 3, France aut NATIONALLICENCE 700 1- Perdu E. INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, 180 chemin de Tournefeuille, BP 93173, 31027, Toulouse Cedex 3, France aut NATIONALLICENCE 700 1- Cravedi J. INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, 180 chemin de Tournefeuille, BP 93173, 31027, Toulouse Cedex 3, France aut NATIONALLICENCE 700 1- Zalko D. INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, 180 chemin de Tournefeuille, BP 93173, 31027, Toulouse Cedex 3, France aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/11(2011-11-01), 1463-1473 0340-5761 85:11<1463 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer