A stable fish reporter cell line to study estrogen receptor transactivation by environmental (xeno)estrogens.

A. Cosnefroy (1) , F. Brion (1) , B. Guillet (1) , N. Laville (1) , J. M. Porcher (1) , P. Balaguer (2) , S. Aït-Aïssa (1)

1 INERIS - Institut National de l'Environnement Industriel et des Risques
2 IRCM - U896 Inserm - UM1 - Institut de recherche en cancérologie de Montpellier

Cross-species differences between human and fish estrogen receptor (ER) binding by environmental chemicals have been reported. To study ER transactivation in a fish cellular context, we stably co-transfected the PLHC-1 fish hepatoma cell line with a rainbow trout estrogen receptor (rtER) and the luciferase reporter gene driven by an estrogen response element (ERE). This new cell model, called PELN-rtER (for PLHC-1-ERE-Luciferase-Neomycin), responded to 17beta-estradiol (E2) in a both concentration- and temperature-dependent manner, as well as to environmental ER ligands from different chemical classes: natural and synthetic estrogens, zearalenone metabolites, genistein, alkyphenoles and benzophenone derivatives. The comparison with other in vitro models, i.e. human reporter cell lines (HELN-rtER, MELN) and vitellogenin induction in primary cultures of rainbow trout hepatocytes, showed an overall higher sensitivity of the human cells for a majority of ligands, except for benzophenone derivatives which were active at similar or lower concentrations in fish cells, suggesting species-specificity for these substances. Correlation analyses suggest that the fish cell line is closer to the trout hepatocyte than to the human cell context, and could serve as a relevant mechanistic tool to study ER activation in fish hepatic cellular context.

Domaines: Toxicologie

A. Cosnefroy, F. Brion, B. Guillet, N. Laville, J. M. Porcher, et al.. A stable fish reporter cell line to study estrogen receptor transactivation by environmental (xeno)estrogens.. Toxicology in Vitro, 2009, 23 (8), pp.1450-4. ⟨10.1016/j.tiv.2009.07.003⟩. ⟨hal-00453656⟩