Platform: Affymetrix GeneChip Human Genome U219

Organism: Homo sapiens

Pdf version of the dendrogram

Set title:

Nanotoxicogenomic study of ZnO and TiO2 responses


Tuomela S, Autio R, Buerki-Thurnherr T, Arslan O et al. Gene expression profiling of immune-competent human cells exposed to engineered zinc oxide or titanium dioxide nanoparticles. PLoS One. 2013 Jul 22;8(7):e68415.

Set summary:

A comprehensive in vitro assessment of two commercial metal oxide nanoparticles, TiO2 and ZnO, was performed using human monocyte-derived macrophages (HMDM), monocyte-derived dendritic cells (MDDC), and T cell leukemia-derived cell line (Jurkat). TiO2 nanoparticles were found to be non-toxic whereas ZnO nanoparticles caused dose-dependent cell death. Subsequently, global gene expression profiling was performed to identify signaling pathways underlying the cytotoxicity caused by ZnO nanoparticles. Analysis was done with doses, 1µg/ml and 10µg/ml after 6 and 24 hours of exposure. Interestingly, 2703 genes were significantly differentially expressed in HMDM upon exposure to 10µg/ml ZnO nanoparticles, while in MDDCs only 12 genes were affected. In Jurkat cells, 980 genes were differentially expressed. It is noteworthy that the gene expression of metallothioneins was upregulated in all the three cell types. In addition to the common ZnO-inducible changes, a notable proportion of the genes were regulated in a cell type-specific manner. Using a panel of ZnO nanoparticles, we obtained an additional support that the cellular response to ZnO nanoparticles is caused by particle dissolution. Gene ontology analysis revealed that the top biological processes disturbed in HMDM and Jurkat cells were regulating cell death and growth. In addition, genes controlling immune system development were affected. Bioinformatics assessment showed that the top human disease category associated with ZnO-responsive genes in both HMDM and Jurkat cells was cancer. Overall, the study revealed novel genes and pathways for mediating ZnO nanoparticle-induced toxicity and demonstrated the value of assessing nanoparticle responses through combined transcriptomics and bioinformatics approach.

Sample_name Description Type Treatment Dose NP_size
GSM961226 HMDM_rep1_ctr_6h_0 HMDM no treatment - -
GSM961234 HMDM_rep2_ctr_6h_0 HMDM no treatment - -
GSM961242 HMDM_rep3_ctr_6h_0 HMDM no treatment - -
GSM961230 HMDM_rep1_ZnO-1_6h_10 HMDM ZnO-1 10µg/ml 10 ± 2nm
GSM961238 HMDM_rep2_ZnO-1_6h_10 HMDM ZnO-1 10µg/ml 10 ± 2nm
GSM961247 HMDM_rep3_ZnO-1_6h_10 HMDM ZnO-1 10µg/ml 10 ± 2nm
GSM961228 HMDM_rep1_ctr_24h_0 HMDM no treatment - -
GSM961236 HMDM_rep2_ctr_24h_0 HMDM no treatment - -
GSM961245 HMDM_rep3_ctr_24h_0 HMDM no treatment - -
GSM961223 HMDM_rep1_ZnO-1_24h_10 HMDM ZnO-1 10µg/ml 10 ± 2nm
GSM961232 HMDM_rep2_ZnO-1_24h_10 HMDM ZnO-1 10µg/ml 10 ± 2nm
GSM961240 HMDM_rep3_ZnO-1_24h_10 HMDM ZnO-1 10µg/ml 10 ± 2nm