Surface modified titanium dioxide nanoparticles induce fibrosis-like changes in lungs at high doses [set 3]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE81566 | GEO | 2016/12/07
SECONDARY ACCESSION(S): PRJNA322018
REPOSITORIES: GEO
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Project description:Previous studies have shown that TiO2NPs induce lung inflammation in mice and have suggested that the degree of inflammation varies with their size and other physical and chemical properties, e.g., shapes, surface modifications and surface charge. It is currently unknown if the observed inflammation in mouse lungs following exposure to TiO2NPs will cause any disease in the long term. This study examined mouse lung responses to six individual TiO2NPs of varying sizes (10, 20 and 300 nm), surface modifications and shapes. C57BL/6 mice were exposed to 18 µg, 54 µg, 162 µg or 486 µg of TiO2NPs/mouse via direct deposition of particles in lungs. Lung fluid and lung tissue were sampled on day 1, day 28 and day 90. Changes in inflammation and gene expression in lung were profiled. Histopathological changes in lungs indicative of diseases were examined by microscopic techniques. The results confirmed that all TiO2NPs induce lung inflammation immediately after exposure. At the highest dose tested, this particular TiO2NPs with surface modification induced signs of lung fibrosis (a disease of regulatory importance for NMs. Although lung response induced by TiO2NPs is influenced by many of their properties, the results of the study indicated that certain surface modification may play role in causing a disease.
2016-12-07 | GSE81569 | GEO
Project description:Previous studies have shown that TiO2NPs induce lung inflammation in mice and have suggested that the degree of inflammation varies with their size and other physical and chemical properties, e.g., shapes, surface modifications and surface charge. It is currently unknown if the observed inflammation in mouse lungs following exposure to TiO2NPs will cause any disease in the long term. This study examined mouse lung responses to six individual TiO2NPs of varying sizes (10, 20 and 300 nm), surface modifications and shapes. C57BL/6 mice were exposed to 18 µg, 54 µg, 162 µg or 486 µg of TiO2NPs/mouse via direct deposition of particles in lungs. Lung fluid and lung tissue were sampled on day 1, day 28 and day 90. Changes in inflammation and gene expression in lung were profiled. Histopathological changes in lungs indicative of diseases were examined by microscopic techniques. The results confirmed that all TiO2NPs induce lung inflammation immediately after exposure. At the highest dose tested, this particular TiO2NPs with surface modification induced signs of lung fibrosis (a disease of regulatory importance for NMs. Although lung response induced by TiO2NPs is influenced by many of their properties, the results of the study indicated that certain surface modification may play role in causing a disease.
2016-12-07 | GSE81568 | GEO
Project description:Previous studies have shown that TiO2NPs induce lung inflammation in mice and have suggested that the degree of inflammation varies with their size and other physical and chemical properties, e.g., shapes, surface modifications and surface charge. It is currently unknown if the observed inflammation in mouse lungs following exposure to TiO2NPs will cause any disease in the long term. This study examined mouse lung responses to six individual TiO2NPs of varying sizes (10, 20 and 300 nm), surface modifications and shapes. C57BL/6 mice were exposed to 18 µg, 54 µg, 162 µg or 486 µg of TiO2NPs/mouse via direct deposition of particles in lungs. Lung fluid and lung tissue were sampled on day 1, day 28 and day 90. Changes in inflammation and gene expression in lung were profiled. Histopathological changes in lungs indicative of diseases were examined by microscopic techniques. The results confirmed that all TiO2NPs induce lung inflammation immediately after exposure. At the highest dose tested, this particular TiO2NPs with surface modification induced signs of lung fibrosis (a disease of regulatory importance for NMs. Although lung response induced by TiO2NPs is influenced by many of their properties, the results of the study indicated that certain surface modification may play role in causing a disease.
2016-12-07 | GSE81567 | GEO
Project description:Previous studies have shown that TiO2NPs induce lung inflammation in mice and have suggested that the degree of inflammation varies with their size and other physical and chemical properties, e.g., shapes, surface modifications and surface charge. It is currently unknown if the observed inflammation in mouse lungs following exposure to TiO2NPs will cause any disease in the long term. This study examined mouse lung responses to six individual TiO2NPs of varying sizes (10, 20 and 300 nm), surface modifications and shapes. C57BL/6 mice were exposed to 18 µg, 54 µg, 162 µg or 486 µg of TiO2NPs/mouse via direct deposition of particles in lungs. Lung fluid and lung tissue were sampled on day 1, day 28 and day 90. Changes in inflammation and gene expression in lung were profiled. Histopathological changes in lungs indicative of diseases were examined by microscopic techniques. The results confirmed that all TiO2NPs induce lung inflammation immediately after exposure. At the highest dose tested, this particular TiO2NPs with surface modification induced signs of lung fibrosis (a disease of regulatory importance for NMs. Although lung response induced by TiO2NPs is influenced by many of their properties, the results of the study indicated that certain surface modification may play role in causing a disease.
2016-12-07 | GSE81565 | GEO
Project description:Previous studies have shown that TiO2NPs induce lung inflammation in mice and have suggested that the degree of inflammation varies with their size and other physical and chemical properties, e.g., shapes, surface modifications and surface charge. It is currently unknown if the observed inflammation in mouse lungs following exposure to TiO2NPs will cause any disease in the long term. This study examined mouse lung responses to six individual TiO2NPs of varying sizes (10, 20 and 300 nm), surface modifications and shapes. C57BL/6 mice were exposed to 18 µg, 54 µg, 162 µg or 486 µg of TiO2NPs/mouse via direct deposition of particles in lungs. Lung fluid and lung tissue were sampled on day 1, day 28 and day 90. Changes in inflammation and gene expression in lung were profiled. Histopathological changes in lungs indicative of diseases were examined by microscopic techniques. The results confirmed that all TiO2NPs induce lung inflammation immediately after exposure. At the highest dose tested, this particular TiO2NPs with surface modification induced signs of lung fibrosis (a disease of regulatory importance for NMs. Although lung response induced by TiO2NPs is influenced by many of their properties, the results of the study indicated that certain surface modification may play role in causing a disease.
2016-12-07 | GSE81564 | GEO
Project description:We examined the use of toxicogenomics data to 1) elucidate the underlying mechanisms of pulmonary responses following exposures to titanium dioxide (TiO2) nanoparticles (NPs) of different size and surface charge, and 2) determine if such responses are influenced by embedding particles in complex paint matrix. Adult C57BL/6 mice were exposed via single intratracheal instillation to three doses of free forms of NRCWE-030 (10.5 nm), NRCWE-025 (38 nm), NRCWE-001 (10 nm, neutral charge) NRCWE-002 (10 nm, positive charge) or to sanding dusts of paint consisting of NRCWE-030+NRCWE-025 or NRCWE-025 alone. Controls were exposed to dispersion medium without NPs. TiO2NPs were characterized for size, surface area, and agglomeration status in the exposure medium. Hyperspectral microscopy was performed to detect TiO2NPs in lungs and to determine the in vivo status of matrix-embedded TiO2NPs. Pulmonary gene expression profiles were generated using DNA microarrays on lung tissues collected at 24 h and 28 d post exposure time points. Bioinformatics tools were used to characterize size and surface property-pertinent effects. The data from 360 individual arrays were collapsed into 567 differentially expressed genes (False discovery rate adjusted P ≤ 0.05 and fold change ≥ 1.5 in any one condition). Unsupervised hierarchical clustering of the 567 genes revealed that TiO2NPs clustered mainly based on the post-exposure time points and then by the particle types. A meta analysis using pathway tools showed that the combination of smaller size and positive surface charge contributes to the potency of TiO2NPs. Although embedding in matrix dampens the overall toxicity of TiO2NPs, the smaller size positively influences the toxicity. Paint matrix itself did not induce any response. Finally, the observed differences in response reflected the differences in severity of the response and not the underlying mechanisms. Thus, transcriptional profiling is an effective tool to determine the important properties responsible for eliciting a response.
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Project description:We examined the use of toxicogenomics data to 1) elucidate the underlying mechanisms of pulmonary responses following exposures to titanium dioxide (TiO2) nanoparticles (NPs) of different size and surface charge, and 2) determine if such responses are influenced by embedding particles in complex paint matrix. Adult C57BL/6 mice were exposed via single intratracheal instillation to three doses of free forms of NRCWE-030 (10.5 nm), NRCWE-025 (38 nm), NRCWE-001 (10 nm, neutral charge) NRCWE-002 (10 nm, positive charge) or to sanding dusts of paint consisting of NRCWE-030+NRCWE-025 or NRCWE-025 alone. Controls were exposed to dispersion medium without NPs. TiO2NPs were characterized for size, surface area, and agglomeration status in the exposure medium. Hyperspectral microscopy was performed to detect TiO2NPs in lungs and to determine the in vivo status of matrix-embedded TiO2NPs. Pulmonary gene expression profiles were generated using DNA microarrays on lung tissues collected at 24 h and 28 d post exposure time points. Bioinformatics tools were used to characterize size and surface property-pertinent effects. The data from 360 individual arrays were collapsed into 567 differentially expressed genes (False discovery rate adjusted P ≤ 0.05 and fold change ≥ 1.5 in any one condition). Unsupervised hierarchical clustering of the 567 genes revealed that TiO2NPs clustered mainly based on the post-exposure time points and then by the particle types. A meta analysis using pathway tools showed that the combination of smaller size and positive surface charge contributes to the potency of TiO2NPs. Although embedding in matrix dampens the overall toxicity of TiO2NPs, the smaller size positively influences the toxicity. Paint matrix itself did not induce any response. Finally, the observed differences in response reflected the differences in severity of the response and not the underlying mechanisms. Thus, transcriptional profiling is an effective tool to determine the important properties responsible for eliciting a response.
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Project description:We examined the use of toxicogenomics data to 1) elucidate the underlying mechanisms of pulmonary responses following exposures to titanium dioxide (TiO2) nanoparticles (NPs) of different size and surface charge, and 2) determine if such responses are influenced by embedding particles in complex paint matrix. Adult C57BL/6 mice were exposed via single intratracheal instillation to three doses of free forms of NRCWE-030 (10.5 nm), NRCWE-025 (38 nm), NRCWE-001 (10 nm, neutral charge) NRCWE-002 (10 nm, positive charge) or to sanding dusts of paint consisting of NRCWE-030+NRCWE-025 or NRCWE-025 alone. Controls were exposed to dispersion medium without NPs. TiO2NPs were characterized for size, surface area, and agglomeration status in the exposure medium. Hyperspectral microscopy was performed to detect TiO2NPs in lungs and to determine the in vivo status of matrix-embedded TiO2NPs. Pulmonary gene expression profiles were generated using DNA microarrays on lung tissues collected at 24 h and 28 d post exposure time points. Bioinformatics tools were used to characterize size and surface property-pertinent effects. The data from 360 individual arrays were collapsed into 567 differentially expressed genes (False discovery rate adjusted P ≤ 0.05 and fold change ≥ 1.5 in any one condition). Unsupervised hierarchical clustering of the 567 genes revealed that TiO2NPs clustered mainly based on the post-exposure time points and then by the particle types. A meta analysis using pathway tools showed that the combination of smaller size and positive surface charge contributes to the potency of TiO2NPs. Although embedding in matrix dampens the overall toxicity of TiO2NPs, the smaller size positively influences the toxicity. Paint matrix itself did not induce any response. Finally, the observed differences in response reflected the differences in severity of the response and not the underlying mechanisms. Thus, transcriptional profiling is an effective tool to determine the important properties responsible for eliciting a response.
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Project description:We examined the use of toxicogenomics data to 1) elucidate the underlying mechanisms of pulmonary responses following exposures to titanium dioxide (TiO2) nanoparticles (NPs) of different size and surface charge, and 2) determine if such responses are influenced by embedding particles in complex paint matrix. Adult C57BL/6 mice were exposed via single intratracheal instillation to three doses of free forms of NRCWE-030 (10.5 nm), NRCWE-025 (38 nm), NRCWE-001 (10 nm, neutral charge) NRCWE-002 (10 nm, positive charge) or to sanding dusts of paint consisting of NRCWE-030+NRCWE-025 or NRCWE-025 alone. Controls were exposed to dispersion medium without NPs. TiO2NPs were characterized for size, surface area, and agglomeration status in the exposure medium. Hyperspectral microscopy was performed to detect TiO2NPs in lungs and to determine the in vivo status of matrix-embedded TiO2NPs. Pulmonary gene expression profiles were generated using DNA microarrays on lung tissues collected at 24 h and 28 d post exposure time points. Bioinformatics tools were used to characterize size and surface property-pertinent effects. The data from 360 individual arrays were collapsed into 567 differentially expressed genes (False discovery rate adjusted P ≤ 0.05 and fold change ≥ 1.5 in any one condition). Unsupervised hierarchical clustering of the 567 genes revealed that TiO2NPs clustered mainly based on the post-exposure time points and then by the particle types. A meta analysis using pathway tools showed that the combination of smaller size and positive surface charge contributes to the potency of TiO2NPs. Although embedding in matrix dampens the overall toxicity of TiO2NPs, the smaller size positively influences the toxicity. Paint matrix itself did not induce any response. Finally, the observed differences in response reflected the differences in severity of the response and not the underlying mechanisms. Thus, transcriptional profiling is an effective tool to determine the important properties responsible for eliciting a response.
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