Project description: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, 1M-BM-5g/ml and 10M-BM-5g/ml after 6 and 24 hours of exposure. Interestingly, 2703 genes were significantly differentially expressed in HMDM upon exposure to 10M-BM-5g/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. Altogether 90 samples were analyzed originating from three biological replicates of HMDM, MDDC or Jurkat cells containg untreated control cells, ZnO or TiO2 treated cells with doses 1M-BM-5g/ml and 10M-BM-5g/ml. The sample timepoints were 6 hours and 24 hours.

Project description:Today, nanoparticles are used in various commercial products. One of the most common nanoparticles is titanium dioxide (TiO2). It has a catalytic activity and UV absorption (λ<400 nm), and it generates reactive oxygen species (ROS). The catalytic activity of TiO2 nanoparticle is capable of killing a wide range of microorganisms. In the environment, nanoparticles form structures consisting of primary particles, and their aggregates and agglomerates. These compounds are defined NOAA (nano-objects, and their aggregates and agglomerates greater than 100 nm). The unique properties of TiO2 nanoparticles can be maintained in the environment, thus, the growing use of TiO2 nanoparticles is raising concerns about the environmental risks. The assessment of biological and ecological effects of TiO2-NOAA is necessary. In our previous study, we assessed the effect of TiO2-NOAA on microbes by using Saccharomyces cerevisiae and Escherichia coli. It was shown that TiO2-NOAA decomposed methylene blue under UV irradiation. It suggested that TiO2-NOAA generated ROS under UV irradiation. However, TiO2-NOAA did not show growth inhibition in minimal agar medium under UV irradiation. By adding TiO2-NOAA in medium, colony formation was observed with UV intensity that inactivates microbes. Moreover, TiO2-NOAA adsorbed microbes. These results suggested that the amount of ROS generated by TiO2-NOAA was not enough to inactivate microbes, and TiO2-NOAA might protect microbes from UV. In this study, we assessed the effect of TiO2-NOAA in more detail by using S. cerevisiae. We used DNA microarray analysis for qualitative assessment. Further, we carried out quantitative assessment by using Real Time RT-PCR method for characteristic genes in DNA microarray analysis. To compare yeast cells in various conditions, six kinds of treatment conditions were prepared (Condition 1. adsorbed fraction to TiO2-NOAA under UV, 2. non-adsorbed fraction to TiO2-NOAA under UV, 3. adsorbed fraction to TiO2-NOAA without UV, 4. non-adsorbed fraction to TiO2-NOAA without UV, 5. irradiated UV and 6. negative control). From the result of DNA microarray analysis, the most number of genes was altered in Condition 1, followed by Condition 3 and 5. The genes related to oxidative stress, and the genes related to synthesis of trehalose and glycogen were significantly up-regulated of yeast cells in Condition 1 and 5, and Condition 1 and 3, respectively. These results suggest that yeast cells suffer oxidative stress by TiO2-NOAA under UV, and they also suffer membrane damage by TiO2-NOAA itself, as a result, they reserve energy sources. From the result of Real Time RT-PCR, genes related to oxidative stress (GRE2, SOD2) were up-regulated in Condition 1 and 3, however, these expression levels in each condition were not significant. And genes related to synthesis of trehalose and glycogen (GSY1, TPS2) were up-regulated in Condition 1 and 3. These results suggest that oxidative stress is caused not by TiO2-NOAA but by UV. It is also suggested that yeast cells were damaged at their membranes by TiO2-NOAA, as a result, genes related to synthesis of trehalose and glycogen were up-regulated. Thus, we suggest that the effect of TiO2-NOAA on yeast cells under UV irradiation is greater due to TiO2-NOAA itself than due to ROS generated by TiO2-NOAA.

Project description: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, 1ug/ml and 10ug/ml after 6 and 24 hours of exposure. Interestingly, 2703 genes were significantly differentially expressed in HMDM upon exposure to 10ug/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. Nanoparticles used in the study: ZnO-1 commercial (IBU-tec advanced materials AG), ZnO-2 (mandelic acid coated ZnO-1), ZnO-3 (mercaptopropyl-trimethoxysilane coated ZnO-1), ZnO-4 (methoxyl coated ZnO), ZnO-5 (diethylene glycol modified ZnO) and ZnO-9 (folic acid modified ZnO). Detailed particle production and characterization data can be found from the articles: Buerki-Thurnherr et al. 2012 Nanotoxicology and Tuomela et al.

Project description: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, 1ug/ml and 10ug/ml after 6 and 24 hours of exposure. Interestingly, 2703 genes were significantly differentially expressed in HMDM upon exposure to 10ug/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. Nanoparticles used in the study: ZnO-1 commercial (IBU-tec advanced materials AG), ZnO-2 (mandelic acid coated ZnO-1), ZnO-3 (mercaptopropyl-trimethoxysilane coated ZnO-1), ZnO-4 (methoxyl coated ZnO), ZnO-5 (diethylene glycol modified ZnO) and ZnO-9 (folic acid modified ZnO). Detailed particle production and characterization data can be found from the articles: Buerki-Thurnherr et al. 2012 Nanotoxicology and Tuomela et al. Altogether 71 samples were analyzed: 3 biological replicates of HMDM samples (untreated control, 10ug/ml of ZnO-1, 6 and 24 hours), 3 biological replicates of MDDC samples (untreated control, 6 and 24 hours), 7 biological replicates of MDDC samples (10ug/ml of ZnO-1, 24 hours), 3 replicates of Jurkat cells (untreated control, 10ug/ml of ZnO-1, 6 and 24 hours), 3 replicates of Jurkat cells (untreated control, 10ug/ml of ZnO-2, ZnO-3, ZnO-5 or ZnO-9, or 10, 25, 50 or 100ug/ml of ZnO-4, 24 hours).

			Action	DRS
	ERR13187557_1.fastq.gz	Fastqsanger.gz
	ERR13187557_2.fastq.gz	Fastqsanger.gz
	ERR13187558_1.fastq.gz	Fastqsanger.gz
	ERR13187558_2.fastq.gz	Fastqsanger.gz
	ERR13187559_1.fastq.gz	Fastqsanger.gz

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EHEC TiO2

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