title: Endoplasmic reticulum stress as a novel cellular response to di (2-ethylhexyl) phthalate exposure.
abstract: Di (2-ethylhexyl) phthalate is a high-production chemical widely used as a plasticizer for polyvinyl chloride products. Due to its ubiquitous presence in environmental compartments and the constant exposure of the general population through ingestion, inhalation, and dermal absorption, this compound has been subjected to extensive in vivo and in vitro toxicological studies. Despite the available information, research on the cytotoxicity of di (2-ethylhexyl) phthalate in mammalian cells is relatively limited.In this paper, an in vitro multi-parametric approach was used to provide further mechanistic data on the toxic activity of this chemical in Vero and HaCaT cells. Our results reveal that a 24 h exposure to di (2-ethylhexyl) phthalate causes, in both cell lines, an inhibition of cell proliferation that was linked to cell cycle delay at the G1 phase. Concomitantly, the tested compound induces mild endoplasmic reticulum stress which leads to an adaptive rather than a pro-apoptotic response in mammalian cells. These findings demonstrate that there are multiple potential cellular targets of di (2-ethylhexyl) phthalate-induced toxicity and the need to develop further experimental studies for the risk assessment of this ubiquitous plasticizer.
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Darwin, 2, 28049 Madrid, Spain. Electronic address: ana.peropadre@uam.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Peropadre
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Darwin, 2, 28049 Madrid, Spain. Electronic address: paloma.fernandez@uam.es.
authors.forename: Paloma
authors.initials: P
authors.lastname: Fernández Freire
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Darwin, 2, 28049 Madrid, Spain. Electronic address: josemanuel.perez@uam.es.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Pérez Martín
authors.affiliation: Grupo de Biología y Toxicología Ambiental, Facultad de Ciencias, Universidad Nacional de Educación a Distancia, UNED, Senda del Rey 9, 28040 Madrid, Spain. Electronic address: oscar.herrero@ccia.uned.es.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Herrero
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Darwin, 2, 28049 Madrid, Spain. Electronic address: mariajose.hazen@uam.es.
authors.forename: María José
authors.initials: MJ
authors.lastname: Hazen
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D014709:Vero Cells
chemical_list: D004051:Diethylhexyl Phthalate
keywords: Cytotoxicity; Di (2-ethylhexyl) phthalate; ER stress; In vitro assays; Mammalian cells; Metabolic disorders