Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

Gorrochategui, Eva; Pérez-Albaladejo, Elisabet; Casas, Josefina; Lacorte, Sílvia; Porte, Cinta

doi:10.1016/J.TAAP.2014.03.012

Title: Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

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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 cellularmore »« less

Authors:

Gorrochategui, Eva; Pérez-Albaladejo, Elisabet ^[1]; Casas, Josefina ^[2]; Lacorte, Sílvia ^[1]; Porte, Cinta ^[1]

Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain)
Department of Biomedicinal Chemistry, IQAC–CSIC, 08034 Barcelona, Catalonia (Spain)

Publication Date:: Sun Jun 01 00:00:00 EDT 2014

OSTI Identifier:: 22439723

Resource Type:: Journal Article

Journal Name:: Toxicology and Applied Pharmacology

Additional Journal Information:: Journal Volume: 277; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; CONCENTRATION RATIO; INHIBITION; LECITHINS; PLACENTA; TOXICITY; UPTAKE

Citation Formats


                    Gorrochategui, Eva, Pérez-Albaladejo, Elisabet, Casas, Josefina, Lacorte, Sílvia, and Porte, Cinta. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells.  United States: N. p., 2014. 
        Web.  doi:10.1016/J.TAAP.2014.03.012.

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                    Gorrochategui, Eva, Pérez-Albaladejo, Elisabet, Casas, Josefina, Lacorte, Sílvia, & Porte, Cinta. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells.  United States.  https://doi.org/10.1016/J.TAAP.2014.03.012

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                    Gorrochategui, Eva, Pérez-Albaladejo, Elisabet, Casas, Josefina, Lacorte, Sílvia, and Porte, Cinta. 2014.  
        "Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells".  United States.  https://doi.org/10.1016/J.TAAP.2014.03.012.

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@article{osti_22439723,

  title        = {Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells},

  author       = {Gorrochategui, Eva and Pérez-Albaladejo, Elisabet and Casas, Josefina and Lacorte, Sílvia and Porte, Cinta},

  abstractNote = {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. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell lipidome.},

  doi          = {10.1016/J.TAAP.2014.03.012},

  url          = {https://www.osti.gov/biblio/22439723},
  journal      = {Toxicology and Applied Pharmacology},

  issn         = {0041-008X},

  number       = 2,

  volume       = 277,

  place        = {United States},

  year         = {Sun Jun 01 00:00:00 EDT 2014},

  month        = {Sun Jun 01 00:00:00 EDT 2014}

}

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