Fiche publication


Date publication

juin 2019

Journal

Toxicology letters

Auteurs

Membres identifiés du Cancéropôle Est :
Pr RIHN Bertrand


Tous les auteurs :
Safar R, Doumandji Z, Saidou T, Ferrari L, Nahle S, Rihn BH, Joubert O

Résumé

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 (IC) of 8.1 μg/mL. Transcriptomic study of cells exposed to two concentrations of ZnO110NP: IC and a quarter of it (IC/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 exposure to ZnONP. On the contrary, at IC 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.

Mots clés

Cytotoxicity, Metallothionein, NM110, PMA-differentiated THP-1 cells, Transcriptome, Zinc oxide nanoparticle

Référence

Toxicol Lett. 2019 Jun 15;308:65-73