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 inhibi…
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PFAS mixtures can alter cellular lipid patterns.
“PFOA, PFOS, and PFBS are considered aromatase inhibitors in placental cells, and PFAS mixtures can alter cellular lipid patterns (Gorrochategui et al., 2014).”
From Exposure to per- and polyfluoroalkyl substances in early pregnancy, risk of gestational diabetes mellitus, potential pathways, and influencing factors in pregnant women: A nested case-control study (2023) · cites this paper as Gorrochategui et al., 2014
PFOA, PFOS, and PFBS are considered aromatase inhibitors in placental cells.
“PFOA, PFOS, and PFBS are considered aromatase inhibitors in placental cells, and PFAS mixtures can alter cellular lipid patterns (Gorrochategui et al., 2014).”
From Exposure to per- and polyfluoroalkyl substances in early pregnancy, risk of gestational diabetes mellitus, potential pathways, and influencing factors in pregnant women: A nested case-control study (2023) · cites this paper as Gorrochategui et al., 2014
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- Authors
- Gorrochategui, E., Pérez-Albaladejo, E., Casas, J., Lacorte, S., & Porte, C.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Institute of Advanced Chemistry of Catalonia (ES)
- Corresponding author
- Porte, Cinta
- Venue
- Toxicology and Applied Pharmacology
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 277
- Issue
- 2
- Pages
- 124-130
- ISSN
- 0041-008X (ISSN-L)
- OpenAlex
- W2051796247
- Cited by
- 168
- References
- 2
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 14 · 2023: 13 · 2022: 19 · 2021: 18 · 2020: 19 · 2019: 13 · 2018: 15 · 2017: 12 · 2016: 7 · 2015: 7 · 2014: 3
- FWCI
- 7.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology and Applied Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Fluorine in Organic Chemistry
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- perfluorinated compounds, perfluorooctanoic acid, PFOS, perfluorobutanesulfonate, perfluorobutanoic acid, perfluorohexanoic acid, perfluorododecanoic acid, perfluorononanoic acid, PFHxS, JEG-3 cells, cytotoxicity, aromatase inhibition, cellular lipid metabolism, phosphatidylcholine, plasmalogens, membrane lipids, differential toxicity, cellular uptake
- MeSH terms
- Aromatase, Biological Transport, Cell Survival, Dose-Response Relationship, Drug, Female, Fluorocarbons, Humans, Placenta, Pregnancy, Structure-Activity Relationship, Time Factors, Molecular Structure, Risk Assessment, Inhibitory Concentration 50, Cell Line, Tumor, Aromatase Inhibitors, Lipid Metabolism, Endocrine Disruptors
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