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Cytotoxicity and inhibition of intercellular interaction in N2a neurospheroids by perfluorooctanoic acid and perfluorooctanesulfonic acid

Title
Cytotoxicity and inhibition of intercellular interaction in N2a neurospheroids by perfluorooctanoic acid and perfluorooctanesulfonic acid
Author(s)
Choi, Seong-KyoonKim, Jung-HeePark, Jin-KyuLee, Kyeong-MinKim, EunjooJeon, Won Bae
Issued Date
2013-10
Citation
Food and Chemical Toxicology, v.60, pp.520 - 529
Type
Article
Author Keywords
Perfluorinated compoundsNeurospheroidsIntercellular communicationDifferentiation markersCaspaseReactive oxygen species
Keywords
RODENT PEROXISOME PROLIFERATORPERFLUORINATED FATTY-ACIDSHEPATOMA HEPG2 CELLSIN-VITRODEVELOPMENTAL NEUROTOXICITYOXIDATIVE STRESSPRIMARY CULTURESNEURONAL CELLSRAT-LIVERSULFONATE
ISSN
0278-6915
Abstract
Effects of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) on the neuronal lineage marker expression, cell-cell interaction, caspase-3 mRNA transcription and reactive oxygen species production by N2a neuronal cells were assesses in 3-dimensional (3D) spheroid cultures, and the cytotoxicity were thoroughly compared with those of a conventional 2D monolayer-based toxicity assay. Increasing concentrations of PFOA or PFOS resulted in an increase in cell death. The half maximal inhibitory concentrations measured with spheroids were approximately one and a half times greater than the respective values for monolayer cells. Necrosis was prevalent in spheroids regardless of the dose, whereas the major injury mechanism in monolayers was dependent on compound concentration. Both PFOA and PFOS inhibited neuronal, astrocyte and oligodendrocyte marker gene expression by monolayers and spheroids grown under undifferentiated and all-. trans-retinoic acid-induced differentiating conditions. In the presence of PFOA or PFOS, expression levels of E-cadherin and connexin-43 mRNAs were significantly downregulated, and spheroids were dissociated into single cell populations, indicating that the compounds affect the synthesis of E-cadherin and connexin-43 at the transcriptional level. Results from 3D cultures may provide an insight into potential inhibitory mode of action on gap junctional intercellular communication. © 2013 Elsevier Ltd.
URI
http://hdl.handle.net/20.500.11750/3199
DOI
10.1016/j.fct.2013.07.070
Publisher
Elsevier Ltd

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