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

Cytotoxicity and inhibition of intercellular interaction in N2a neurospheroids by perfluorooctanoic acid and perfluorooctanesulfonic acid
Choi, SK[Choi, Seong-Kyoon]Kim, JH[Kim, Jung-Hee]Park, JK[Park, Jin-Kyu]Lee, KM[Lee, Kyeong-Min]Kim, E[Kim, Eunjoo]Jeon, WB[Jeon, Won Bae]
DGIST Authors
Choi, SK[Choi, Seong-Kyoon]; Kim, JH[Kim, Jung-Hee]; Park, JK[Park, Jin-Kyu]; Lee, KM[Lee, Kyeong-Min]; Kim, E[Kim, Eunjoo]Jeon, WB[Jeon, Won Bae]
Issue Date
Food and Chemical Toxicology, 60, 520-529
Article Type
Alkanesulfonic AcidsAnimal CellAnimalsAstrocyteCadherinsCaprylatesCaspaseCaspase 3Cell AdhesionCell AssayCell DifferentiationCell InteractionCell Line, TumorCell LineageCell MarkerCell ProliferationCell Strain N2ACell SurvivalConcentration ResponseConnexin 43Controlled StudyCytotoxicityDifferentiation MarkersDown-RegulationEscherichia ColiFluorocarbonsGap JunctionsGene ExpressionInhibitory Concentration 50Intercellular CommunicationIntermethod ComparisonMessenger RNAMiceMonolayer CultureMouseNerve CellNerve Cell CultureNerve Cell DifferentiationNerve Cell InhibitionNerve Cell NecrosisNeuroblastoma CellNeuronsNeurospheroidsNeurotoxicityNon-HumanOligodendrogliaPerfluorinated CompoundsPerfluorooctanesulfonic AcidPerfluorooctanoic AcidProtein ExpressionProtein SynthesisReactive Oxygen MetaboliteReactive Oxygen Species (ROS)Retinoic AcidRNA TranscriptionRNA, MessengerSpheroid CellSpheroids, CellularToxicity TestingTretinoinTumor Cell LineUvomorulin
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.
Elsevier Ltd
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Companion Diagnostics and Medical Technology Research Group1. Journal Articles

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