Project description:To investigate the patterns of global gene expression profiles modulated by the ZnO nanoparticles and ZnSO4, and to differentiate their modes of toxicity, zebrafish (Danio rerio) will be exposed to the ZnO nanoparticles and ZnSO4 (LC25), and used for microarray analysis by Agilent Zebrafish Oligo Microarray system. 244 genes overlaped between ZnO nanopartices and ZnSO4 treatments in a total of 1,586 differential expressed genes.G-protein coupled receptor protein (GPCR)-signaling pathways, cell-surface receptor-linked signal transduction and immune response are most significant GO terms enriched in genes up regulated by two treatments. Cytokine-cytokine receptor interactions pathway and intestinal immune network for IgA production pathway were enriched among ZnO nanoparticles activated genes, and specifically induced by ZnSO4 include cell adhesion molecules (CAMs) pathway.
Project description:ZnO nanoparticles can elicit a range of perturbed cell responses in vitro. The liver is a target for ZnO nanoparticle-, or Zn2+ released from ZnO nanoparticles-induced accumulation and/or impact in vitro and in vivo. The response of human hepatic stellate cells to ZnO nanoparticles has not yet been assessed. We aimed to determine whether the presence of surface coatings could protect human hepatic stellate cells from ZnO nanoparticle-induced cytotoxicity. Primary human hepatic stellate cells were treated with one of two types of uncoated ZnO nanoparticles (Z-COTE or Nanosun), two types of coated ZnO nanoparticles (HP1, MAX), a mass equivalent of ZnSO4, or were left untreated. After 24 h, RNA was isolated and processed for whole genome transcriptional profiling, comparing the expresson profiles of treated cells to the untreated controls. Each treatment was prepared in duplicate.
Project description:Zinc Oxide nanoparticles (ZnO NPs) are being rapidly developed for use in consumer products, wastewater treatment and chemotherapy providing several possible routes for ZnO NP exposure to humans and aquatic organisms. Recent studies have shown that ZnO NPs undergo rapid dissolution to Zn+2, but the relative contribution of Zn+2 to ZnO NP bioavailability and toxicity is not clear. Gene expression profiling of D. magna exposed to ZnO NPs or ZnSO4 at equitoxic concentrations demonstrated that the particles cause toxicity through a distinct mechanism compared with Zn+2. D. magna were also exposed to a SiO NPs as a particle control at equimolar concentrations. The SiO NPs resulted in few differentially expressed genes and there was very little overlap between the genes affected by the ZnO NPs and the SiO NPs, suggesting that ZnO NPs cause a distinct pattern of differentially expressed genes. In the ZnO NP exposures, effects were observed to genes involved in cytoskeletal transport, cellular respiration and reproduction. Three biomarker genes including a multi-cystatin, ferritin and a C1q containing gene were confirmed as differentially expressed in a specific pattern by ZnO NP and provide a suite of biomarkers for identifying environmental exposure to ZnO NP and differentiating between NP and ionic exposure. We exposed Daphnia magna to the 1/10 LC50 and LC25 of ZnO nanoparticles and Zn++ as ZnSO4 for 24-h. For each exposure condition, we performed 3 exposures and 2 technical replicates (as dye swap) for each exposure (6 microarrays total). All exposures were compared to a unexposed laboratory control
Project description:Engineered nanoparticles (ENPs) are increasingly used to generate innovative industrial and medical goods. Because of their broad applications, they form a new class of pollutants with potential eco-toxicological impacts on marine ecosystems. Attempting to evaluate the risk, we investigated the toxicity of Iron and Zinc oxide ENPs on Paracentrotus lividus sea urchin embryos. Sea urchin embryos are sensitive to both ENPs with a much stronger impact of ZnO ENPs. Transcriptome-wide analyses were conducted after exposure to ENPs or the corresponding ions. Only a very limited number of genes are differentially expressed in response to Fe2O3 ENPs or FeCl3. In contrast, both ZnO ENPs and ZnSO4 caused alteration of biological processes with stronger perturbation of gene expression for the ionic form (higher LFC). Comparison of GO term enrichment of the differentially expressed genes indicated that ENP and ions elicited partly different mechanisms, suggesting that a nanoparticule-dependent response was induced. Remarkably, the expression of the metal binding and ROS scavenging Metallothioneins were massively induced by ZnO ENPs and ZnSO4 while ZnO ENPs and ions mainly repressed the transcription regulation processes which control embryo development.
Project description:There is still a lot of contradiction on whether metal ions are solely responsible for the observed the toxicity of ZnO and CuO nanoparticles to aquatic species. While most tests have studied nanoparticle effects at organismal levels (e.g. mortality, reproduction), effects at suborganismal levels may clarify the role of metal ions, nanoparticles and nanoparticle aggregates. In this study, the effect of ZnO, CuO nanoparticles and zinc, copper salts was tested on the gene expression levels in Daphnia magna. D. magna was exposed during 96 hours to 10% immobilization concentrations of all chemicals, after which daphnids were sampled for a differential gene expression analysis using microarray. When comparing the nanoparticle exposed daphnids (ZnO or CuO) to the metal salt exposed daphnids (zinc or copper salt), the microarray results showed no significantly differentially expressed genes. These results indicate that the toxicity of the tested ZnO and CuO nanoparticles to D. magna caused is solely caused by toxic metal ions. 4 replicate exposures of ZnO nanoparticles, ZnCl2, Blank (for Zn); 4 replicate exposures of CuO nanoparticles, CuCl2.2H2O, Blank (for Cu); Individual reference design with swapped dyes for zinc (e.g. ZnO-REFZn; REFZn-bl) and copper exposure (e.g. CuO-REFCu; REFCu-bl); Zinc reference sample is a mixture of equal aliquots of ZnO nanoparticle, ZnCl2 and blank; Copper reference sample is a mixture of equal aliquots of CuO nanoparticle, CuCl2.2H2O and blank
Project description:There is still a lot of contradiction on whether metal ions are solely responsible for the observed the toxicity of ZnO and CuO nanoparticles to aquatic species. While most tests have studied nanoparticle effects at organismal levels (e.g. mortality, reproduction), effects at suborganismal levels may clarify the role of metal ions, nanoparticles and nanoparticle aggregates. In this study, the effect of ZnO, CuO nanoparticles and zinc, copper salts was tested on the gene expression levels in Daphnia magna. D. magna was exposed during 96 hours to 10% immobilization concentrations of all chemicals, after which daphnids were sampled for a differential gene expression analysis using microarray. When comparing the nanoparticle exposed daphnids (ZnO or CuO) to the metal salt exposed daphnids (zinc or copper salt), the microarray results showed no significantly differentially expressed genes. These results indicate that the toxicity of the tested ZnO and CuO nanoparticles to D. magna caused is solely caused by toxic metal ions. 4 replicate exposures of ZnO nanoparticles, ZnCl2, Blank (for Zn); 4 replicate exposures of CuO nanoparticles, CuCl2.2H2O, Blank (for Cu); Individual reference design with swapped dyes for zinc (e.g. ZnO-REFZn; REFZn-bl) and copper exposure (e.g. CuO-REFCu; REFCu-bl); Zinc reference sample is a mixture of equal aliquots of ZnO nanoparticle, ZnCl2 and blank; Copper reference sample is a mixture of equal aliquots of CuO nanoparticle, CuCl2.2H2O and blank
Project description:Zinc Oxide nanoparticles (ZnO NPs) are being rapidly developed for use in consumer products, wastewater treatment and chemotherapy providing several possible routes for ZnO NP exposure to humans and aquatic organisms. Recent studies have shown that ZnO NPs undergo rapid dissolution to Zn+2, but the relative contribution of Zn+2 to ZnO NP bioavailability and toxicity is not clear. Gene expression profiling of D. magna exposed to ZnO NPs or ZnSO4 at equitoxic concentrations demonstrated that the particles cause toxicity through a distinct mechanism compared with Zn+2. D. magna were also exposed to a SiO NPs as a particle control at equimolar concentrations. The SiO NPs resulted in few differentially expressed genes and there was very little overlap between the genes affected by the ZnO NPs and the SiO NPs, suggesting that ZnO NPs cause a distinct pattern of differentially expressed genes. In the ZnO NP exposures, effects were observed to genes involved in cytoskeletal transport, cellular respiration and reproduction. Three biomarker genes including a multi-cystatin, ferritin and a C1q containing gene were confirmed as differentially expressed in a specific pattern by ZnO NP and provide a suite of biomarkers for identifying environmental exposure to ZnO NP and differentiating between NP and ionic exposure.
Project description:Abstract: Nanoparticles (NPs) are expected to make their way into the aquatic environment where sedimentation of particles will likely occur, putting benthic organisms at particular risk. Therefore, organisms such as Hyalella azteca, an epibenthic crustacean which forages at the sediment surface, is likely to have a high potential exposure. Here we show that Zinc Oxide (ZnO) NPs are more toxic to H. azteca compared with the corresponding metal ion, Zn2+. Dissolution of ZnO NPs contributes about 50% of the Zn measured in the ZnO NP suspensions, and cannot account for the toxicity of these particles to H. azteca. However, gene expression analysis is unable to distinguish between the ZnO NP exposures and Zinc Sulfate (ZnSO4) exposures at equitoxic concentrations. These results lead us to hypothesize that ZnO NPs provide and an enhanced exposure route for Zn2+ uptake into H. azteca, and possibly other sediment dwelling organisms. Our study supports the prediction that sediment dwelling organisms are highly susceptible to the effects of ZnO NPs and should be considered in the risk assessment of these nanomaterials.
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.