Cytotoxicity and global transcriptional responses induced by zinc oxide nanoparticles NM 110 in PMA-differentiated THP-1 cells

Autor: Safar, Ramia, Doumandji, Zahra, Saidou, Timeh, Ferrari, Luc, Nahle, Sara, Rihn, Bertrand, Joubert, Olivier
Přispěvatelé: Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), CCSD, Accord Elsevier, Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Toxicology Letters
Toxicology Letters, 2019, 308, pp.65-73. ⟨10.1016/j.toxlet.2018.11.003⟩
Toxicology Letters, Elsevier, 2019, 308, pp.65-73. ⟨10.1016/j.toxlet.2018.11.003⟩
ISSN: 0378-4274
1879-3169
DOI: 10.1016/j.toxlet.2018.11.003⟩
Popis: International audience; Despite a wide production and use of zinc oxide nanoparticles (ZnONP), their toxicological study is only of limited number and their impact at a molecular level is seldom addressed. Thus, we have used, as a model, zinc oxide nanoparticle NM110 (ZnO110NP) exposure to PMA-differentiated THP-1 macrophages. The cell viability was studied at the cellular level using WST-1, LDH and Alamar Blue® assays, as well as at the molecular level by transcriptomic analysis. Exposure of cells to ZnO110NP for 24 h decreased their viability in a dose-dependent manner with mean inhibitory concentrations (IC50) of 8.1 µg/mL. Transcriptomic study of cells exposed to two concentrations of ZnO110NP: IC50 and a quarter of it (IC50/4) for 4 h showed that the expressions of genes involved in metal metabolism are perturbed. In addition, expression of genes acting in transcription regulation and DNA binding, as well as clusters of genes related to protein synthesis and structure were altered. It has to be noted that the expressions of metallothioneins genes (MT1, MT2) and genes of heat-shock proteins genes (HSP) were strongly upregulated for both conditions. These genes might be used as an early marker of exposition to ZnONP. On the contrary, at IC50 exposure, modifications of gene expression involved in inflammation, apoptosis and mitochondrial suffering were noted indicating a less specific cellular response. Overall, this study brings a resource of transcriptional data for ZnONP toxicity for further mechanistic studies.
Databáze: OpenAIRE
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