Platform: Illumina Sentrix HumanHT-12 Expression BeadChips, version 3

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
GSM960827 Jurkat_rep1_ctr_6h_0 Jurkat no treatment - -
GSM960837 Jurkat_rep2_ctr_6h_0 Jurkat no treatment - -
GSM960847 Jurkat_rep3_ctr_6h_0 Jurkat no treatment - -
GSM960829 Jurkat_rep1_TiO2_6h_1 Jurkat TiO2 1µg/ml 21nm
GSM960839 Jurkat_rep2_TiO2_6h_1 Jurkat TiO2 1µg/ml 21nm
GSM960849 Jurkat_rep3_TiO2_6h_1 Jurkat TiO2 1µg/ml 21nm
GSM960830 Jurkat_rep1_TiO2_6h_10 Jurkat TiO2 10µg/ml 21nm
GSM960840 Jurkat_rep2_TiO2_6h_10 Jurkat TiO2 10µg/ml 21nm
GSM960850 Jurkat_rep3_TiO2_6h_10 Jurkat TiO2 10µg/ml 21nm
GSM960833 Jurkat_rep1_ZnO_6h_1 Jurkat ZnO 1µg/ml 10 ± 2nm
GSM960843 Jurkat_rep2_ZnO_6h_1 Jurkat ZnO 1µg/ml 10 ± 2nm
GSM960853 Jurkat_rep3_ZnO_6h_1 Jurkat ZnO 1µg/ml 10 ± 2nm
GSM960834 Jurkat_rep1_ZnO_6h_10 Jurkat ZnO 10µg/ml 10 ± 2nm
GSM960844 Jurkat_rep2_ZnO_6h_10 Jurkat ZnO 10µg/ml 10 ± 2nm
GSM960854 Jurkat_rep3_ZnO_6h_10 Jurkat ZnO 10µg/ml 10 ± 2nm
GSM960828 Jurkat_rep1_ctr_24h_0 Jurkat no treatment - -
GSM960838 Jurkat_rep2_ctr_24h_0 Jurkat no treatment - -
GSM960848 Jurkat_rep3_ctr_24h_0 Jurkat no treatment - -
GSM960831 Jurkat_rep1_TiO2_24h_1 Jurkat TiO2 1µg/ml 21nm
GSM960841 Jurkat_rep2_TiO2_24h_1 Jurkat TiO2 1µg/ml 21nm
GSM960851 Jurkat_rep3_TiO2_24h_1 Jurkat TiO2 1µg/ml 21nm
GSM960832 Jurkat_rep1_TiO2_24h_10 Jurkat TiO2 10µg/ml 21nm
GSM960842 Jurkat_rep2_TiO2_24h_10 Jurkat TiO2 10µg/ml 21nm
GSM960852 Jurkat_rep3_TiO2_24h_10 Jurkat TiO2 10µg/ml 21nm
GSM960835 Jurkat_rep1_ZnO_24h_1 Jurkat ZnO 1µg/ml 10 ± 2nm
GSM960845 Jurkat_rep2_ZnO_24h_1 Jurkat ZnO 1µg/ml 10 ± 2nm
GSM960855 Jurkat_rep3_ZnO_24h_1 Jurkat ZnO 1µg/ml 10 ± 2nm
GSM960836 Jurkat_rep1_ZnO_24h_10 Jurkat ZnO 10µg/ml 10 ± 2nm
GSM960846 Jurkat_rep2_ZnO_24h_10 Jurkat ZnO 10µg/ml 10 ± 2nm
GSM960856 Jurkat_rep3_ZnO_24h_10 Jurkat ZnO 10µg/ml 10 ± 2nm