title: Perfluorinated chemicals: differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells.
abstract: The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs--PFOS, PFDoA, PFNA, PFOA--showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA>PFOS≫PFNA>PFOA>PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57-80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells.
authors.affiliation: Department of Environmental Chemistry, IDAEA-CSIC, 08034 Barcelona, Catalonia, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Gorrochategui
authors.affiliation: Department of Environmental Chemistry, IDAEA-CSIC, 08034 Barcelona, Catalonia, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Pérez-Albaladejo
authors.affiliation: Department of Biomedicinal Chemistry, IQAC-CSIC, 08034 Barcelona, Catalonia, Spain.
authors.forename: Josefina
authors.initials: J
authors.lastname: Casas
authors.affiliation: Department of Environmental Chemistry, IDAEA-CSIC, 08034 Barcelona, Catalonia, Spain. Electronic address: slbqam@cid.csic.es.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Lacorte
authors.affiliation: Department of Environmental Chemistry, IDAEA-CSIC, 08034 Barcelona, Catalonia, Spain. Electronic address: cinta.porte@cid.csic.es.
authors.forename: Cinta
authors.initials: C
authors.lastname: Porte
mesh_terms: D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D020128:Inhibitory Concentration 50; D050356:Lipid Metabolism / Q000187:drug effects*; D015394:Molecular Structure; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D011247:Pregnancy; D018570:Risk Assessment; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D047072:Aromatase Inhibitors; D052244:Endocrine Disruptors; D005466:Fluorocarbons; D001141:Aromatase
keywords: CYP19; Cytotoxicity; JEG-3; PFBS; Perfluorinated chemicals; Phosphatidylcholines