title: Differentiation of PC12 cells expressing estrogen receptor alpha: a new bioassay for endocrine-disrupting chemicals evaluation.
abstract: Xeno-estrogens, a class of endocrine disrupting chemicals (EDCs), can disturb estrogen receptor-dependent pathways involved in differentiation, proliferation or protection. Multiple methods have been developed to characterize the disturbances induced by EDCs in different cells or organs. In this study we have developed a new tool for the assessment of estrogenic compounds on differentiation. For this purpose we used the global model of NGF-induced neurite outgrowth of a pseudoneuronal PC12 cell line stably transfected with estrogen receptor alpha (PC12 ER). This new test evidences a new selectivity in which estradiol, genistein and 4-hydroxytamoxifen increased the NGF-induced neurite outgrowth of PC12 ER cells in a dose-dependent manner. In contrast, the strong estrogen agonist 17α-ethynylestradiol, the strong antagonist raloxifene and the agonist bisphenol A were unable to modify the neuritogenesis of PC12 ER cells. Therefore, the analysis of neuritogenesis in PC12 ER cells constitutes a complementary tool for the characterization of xeno-estrogen activity and also serves as a basis for further studies focusing on the mechanisms of EDCs in a neuronal context. Moreover, this test constitutes an alternative to animal testing.
authors.affiliation: Institut de Recherche en Santé Environnement et Travail (IRSET), INSERM U1085, Equipe TREC, Université de Rennes 1, SFR Biosit, Rennes, France. Electronic address: denis.habauzit@univ-rennes1.fr.
authors.forename: Denis
authors.initials: D
authors.lastname: Habauzit
authors.affiliation: Institut de Recherche en Santé Environnement et Travail (IRSET), INSERM U1085, Equipe TREC, Université de Rennes 1, SFR Biosit, Rennes, France.
authors.forename: François
authors.initials: F
authors.lastname: Ferrière
authors.affiliation: Institut de Recherche en Santé Environnement et Travail (IRSET), INSERM U1085, Equipe TREC, Université de Rennes 1, SFR Biosit, Rennes, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Botherel
authors.affiliation: Institut de Recherche en Santé Environnement et Travail (IRSET), INSERM U1085, Equipe TREC, Université de Rennes 1, SFR Biosit, Rennes, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Flouriot
authors.affiliation: Institut de Recherche en Santé Environnement et Travail (IRSET), INSERM U1085, Equipe TREC, Université de Rennes 1, SFR Biosit, Rennes, France. Electronic address: farzad.pakdel@univ-rennes1.fr.
authors.forename: Farzad
authors.initials: F
authors.lastname: Pakdel
authors.affiliation: Institut de Recherche en Santé Environnement et Travail (IRSET), INSERM U1085, Equipe TREC, Université de Rennes 1, SFR Biosit, Rennes, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Saligaut
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects*; D052244:Endocrine Disruptors / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000633:toxicity*; D015870:Gene Expression; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D004967:Estrogens
keywords: Differentiation; Endocrine-disrupting chemicals; Estrogen; Estrogen receptor; PC12 cells