Document Detail

Biotransformation of genistein and bisphenol A in cell lines used for screening endocrine disruptors.
MedLine Citation:
PMID:  18640261     Owner:  NLM     Status:  MEDLINE    
In vitro assays provide the opportunity for generating alerts for chemicals which interact with hormone receptors and are also valuable tools for mechanistic research. However, the limited capabilities of in vitro models to metabolically activate or inactivate xenobiotics may lead to misinterpretation of the in vitro data if such information is not taken into account. The aim of this study was to investigate the metabolic capabilities of human HepG2, human MCF7 and mouse HC11 cell lines used for testing endocrine disruptors (EDs) toward radiolabelled bisphenol A and genistein, two estrogenic compounds for which metabolic pathways in vivo as in vitro are well known. Incubations were performed during 12-48 h with 250.10(3) cells in 12 wells plates and 5-25 microM of substrates. The kinetics of formation of the metabolites were studied. Rat liver slices were used as reference for comparison with the metabolic capabilities of the cell lines. HC11 cells did not show any biotransformation capability while the major biotransformation pathways in HepG2 and MCF7 cells were conjugation to sulfate and to a lesser extent to glucuronic acid. We detected no phase I metabolite, even in rat liver slices. These results suggest that HC11 cells should be a valuable cellular system to study the intrinsic estrogenic activity of the tested compound, while HepG2 and MCF7 cells can help to take into account part of the metabolic fate of the tested compound that occur in vivo. However, since phase I enzymes are poorly or not at all expressed in these systems, their use in endocrine disruptor testing may result in false negative for compounds for which bioactivation is a prerequisite.
J Bursztyka; E Perdu; K Pettersson; I Pongratz; M Fernández-Cabrera; N Olea; L Debrauwer; D Zalko; J P Cravedi
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-02
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  22     ISSN:  0887-2333     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-18     Completed Date:  2008-10-21     Revised Date:  2009-04-10    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  1595-604     Citation Subset:  IM    
Institut National de la Recherche Agronomique, UMR 1089 Xénobiotiques, Toulouse CEDEX 9, France.
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MeSH Terms
Cell Line
Cell Line, Tumor
Endocrine Disruptors / metabolism*
Genistein / metabolism*
Glucuronates / chemistry
Liver / metabolism
Models, Biological
Phenols / metabolism*
Rats, Wistar
Sulfates / chemistry
Time Factors
Reg. No./Substance:
0/Endocrine Disruptors; 0/Glucuronates; 0/Phenols; 0/Sulfates; 446-72-0/Genistein; 80-05-7/bisphenol A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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