Transcriptomic analysis of mouse lung tissue exposed to two multiwalled carbon nanotubes (NRCWE-26 and NM-401)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE55286 | GEO | 2015/02/18
SECONDARY ACCESSION(S): PRJNA239202
REPOSITORIES: GEO
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Project description:Multi-walled carbon nanotubes (MWCNTs) are extensively produced and used in composite materials and electronic applications, thus increasing risk of worker and consumer exposure. MWCNTs are an inhomogeneous group of nanomaterials that exist in various lengths, shapes and with different metal compositions, which makes hazard evaluation difficult. However, several studies suggest that length plays an important role in the toxicity induced by MWCNTs. How the length influences toxicity at the molecular level is yet to be characterized. We used high-content genomics tools to compare pulmonary responses after exposure to a short, entangled MWCNT to the pulmonary responses after exposure to a long, stiffer MWCNT at the global transcriptomic level. Female C57BL/6 mice were exposed by single intratracheal instillation to 18, 54 or 162 M-BM-5g/mouse of a short MWCNT (NRCWE-26 (NC-7000), 847M-BM-1102 nm in length) or long MWCNT (NM-401 (CP-0006-SG), 4048M-BM-1366 nm in length). Lung tissues were harvested 24 h, 3 d and 28 d after exposure. This experiment examined the pulmonary transcriptional response of female C57BL/6 mice exposed to NRCWE-26, a short multi-walled carbon nanotube, and NM-401, a long multi-walled carbon nanotube, at three doses: D1 (18 M-NM-<g), D2 (54 M-NM-<g), D3 (162 M-NM-<g), and vehicle control. Each dose group was examined 1, 3 or 28 days post-exposure. Each dose group had 5-6 biological replicates. There were a total of 139 samples included in the final analysis using a two-color reference design.
2015-02-18 | E-GEOD-55286 | biostudies-arrayexpress
Project description:Adverse lung effects in rodents following pulmonary exposure to multi-walled carbon nanotubes (MWCNT) are well documented. However, systemic effects are less understood. Prospective epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNT might pose similar risks. We used high-content genomics tools to compare hepatic responses after exposure to a short, entangled MWCNT to the hepatic responses after exposure to a long, stiffer MWCNT at the global transcriptomic level. Female C57BL/6 mice were exposed by single intratracheal instillation to 162 M-BM-5g/mouse of a short MWCNT (NRCWE-26 (NC-7000), 847M-BM-1102 nm in length) or long MWCNT (NM-401 (CP-0006-SG), 4048M-BM-1366 nm in length). Liver tissues were harvested 24 h, 3 d and 28 d after exposure. This experiment examined the pulmonary transcriptional response of female C57BL/6 mice exposed to NRCWE-26, a short multi-walled carbon nanotube, and NM-401, a long multi-walled carbon nanotube, at three doses: D1 (18 M-NM-<g), D2 (54 M-NM-<g), D3 (162 M-NM-<g), and vehicle control. Each dose group was examined 1, 3 or 28 days post-exposure. Each dose group had 6 biological replicates. There were a total of 72 samples included in the final analysis using a two-color reference design.
2015-02-02 | E-GEOD-61366 | biostudies-arrayexpress
Project description:Adverse lung effects in rodents following pulmonary exposure to multi-walled carbon nanotubes (MWCNT) are well documented. However, systemic effects are less understood. Prospective epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNT might pose similar risks. We used high-content genomics tools to compare hepatic responses after exposure to a short, entangled MWCNT to the hepatic responses after exposure to a long, stiffer MWCNT at the global transcriptomic level. Female C57BL/6 mice were exposed by single intratracheal instillation to 162 µg/mouse of a short MWCNT (NRCWE-26 (NC-7000), 847±102 nm in length) or long MWCNT (NM-401 (CP-0006-SG), 4048±366 nm in length). Liver tissues were harvested 24 h, 3 d and 28 d after exposure.
2015-02-02 | GSE61366 | GEO
Project description:Carbon nanotubes (CNTs) are newly developed nanomaterials with unique chemical and physical properties. Exposure to airborne CNTs in occupational settings or via consumer products is expected to increase significantly within the next decade due to the vigorous synthesis and applications of these materials in numerous consumer and industrial activities. Previous studies have shown that multiwalled CNT (MWCNT) induce pulmonary inflammation and pulmonary fibrosis. In the present study, we investigated genotoxic potential of MWCNTs. Female MutaMouse were exposed to 42.7 ug/mouse or 128 ug/mouse doses of MWCNTs Mitsui XNRi-7 or NM 401 once a week for four consecutive weeks. Doses were administered via intratracheal instillation. Lung tissues were collected 56 days post-exposure. Bronchoalveolar lavage(BAL) fluid cellularity, BAL and lung tissue DNA damage (COMET assay), lacz mutation frequency and global gene expression changes in lung tissue were determined.
2015-11-27 | GSE75429 | GEO
Project description:Multi-walled carbon nanotubes (MWCNTs) are among the most promising nanomaterials because of their physical and chemical properties. However, since they are biopersistent fiber-like materials which share similarities with asbestos, concerns have arisen about their health effects. With their various industrial usages, occupational exposure to MWCNTs may occur mainly by inhalation as these nanomaterials can get aerosolised. The number of toxicological studies on CNTs has steadily increased for the last decades. Different works showed that MWCNT exposure by inhalation or intratracheal instillation could lead to pulmonary toxicity, such as lung inflammation, genotoxicity, fibrosis or lung cancer (Kasai et al. 2015, Kasai et al. 2016, Porter et al. 2013, Suzui et al. 2016). To date, only one MWCNT (MWNT-7) has been classified as possibly carcinogen to human (Group 2B) while the others have not been as classifiable as to their carcinogenicity to humans (Group 3) because of the lack of data on their carcinogenic potential (IARC 2017). Because of the wide variety of CNTs with various length, diameter or functionalisation, additional effort is required to assess their pulmonary toxicity. As a complementary approach to conventional toxicological assays, the omics methods are useful technologies for the mechanistic understanding of the toxicological effects observed following exposure to chemicals and particulate matters. Importantly, they can also be used as predictive tools for identifying the mode of action of other particles with similar physical and chemical characteristics. These molecular approaches may also be used for the discovery of exposure markers or early markers of adverse effects, before the appearance of clinical signs of a disease (Rahman et al. 2017). Several studies assessed gene expression alteration following in vivo exposure to CNTs (Poulsen et al. 2015, Snyder-Talkington et al. 2013, Ellinger-Ziegelbauer and Pauluhn 2009). These omics approaches were used to identify genes and pathways modulated in response to exposure. However, there are still too few studies to assess the link between MWCNT physico-chemical properties, global gene or protein expression profiles, and long-term effects. In a previous study, we showed that inhalation of two pristine MWCNTs, the long and thick NM-401, and the short and thin NM-403, induced alveolar neutrophilic granulocyte influx, a hallmark of inflammation, which was proportional to the lung CNT BET surface deposited dose (Gate et al. 2019). However, due to their different physical and chemical properties, one could assume that these two CNTs may have diverse toxicological profiles, but the conventional toxicology approaches used in this early work were probably not sensitive enough to identify such differences. In order to gain additional insight about their toxicological properties, in the current study, we compare the alteration induced by the two MWCNTs on the transcriptome in the lung tissue and the proteome in the broncho-alveolar lavage fluid (BALF) after rat exposure by inhalation. The omics analyses were performed from 3 days up to 180 days.
2021-11-22 | PXD029842 | Pride
Project description:Multi-walled carbon nanotubes (MWCNTs) are among the most promising nanomaterials because of their physical and chemical properties. However, since they are biopersistent fiber-like materials which share similarities with asbestos, concerns have arisen about their health effects. With their various industrial usages, occupational exposure to MWCNTs may occur mainly by inhalation as these nanomaterials can get aerosolised. The number of toxicological studies on CNTs has steadily increased for the last decades. Different works showed that MWCNT exposure by inhalation or intratracheal instillation could lead to pulmonary toxicity, such as lung inflammation, genotoxicity, fibrosis or lung cancer (Kasai et al. 2015, Kasai et al. 2016, Porter et al. 2013, Suzui et al. 2016). To date, only one MWCNT (MWNT-7) has been classified as possibly carcinogen to human (Group 2B) while the others have not been as classifiable as to their carcinogenicity to humans (Group 3) because of the lack of data on their carcinogenic potential (IARC 2017). Because of the wide variety of CNTs with various length, diameter or functionalisation, additional effort is required to assess their pulmonary toxicity. As a complementary approach to conventional toxicological assays, the omics methods are useful technologies for the mechanistic understanding of the toxicological effects observed following exposure to chemicals and particulate matters. Importantly, they can also be used as predictive tools for identifying the mode of action of other particles with similar physical and chemical characteristics. These molecular approaches may also be used for the discovery of exposure markers or early markers of adverse effects, before the appearance of clinical signs of a disease (Rahman et al. 2017). Several studies assessed gene expression alteration following in vivo exposure to CNTs (Poulsen et al. 2015, Snyder-Talkington et al. 2013, Ellinger-Ziegelbauer and Pauluhn 2009). These omics approaches were used to identify genes and pathways modulated in response to exposure. However, there are still too few studies to assess the link between MWCNT physico-chemical properties, global gene or protein expression profiles, and long-term effects. In a previous study, we showed that inhalation of two pristine MWCNTs, the long and thick NM-401, and the short and thin NM-403, induced alveolar neutrophilic granulocyte influx, a hallmark of inflammation, which was proportional to the lung CNT BET surface deposited dose (Gate et al. 2019). However, due to their different physical and chemical properties, one could assume that these two CNTs may have diverse toxicological profiles, but the conventional toxicology approaches used in this early work were probably not sensitive enough to identify such differences. In order to gain additional insight about their toxicological properties, in the current study, we compare the alteration induced by the two MWCNTs on the transcriptome in the lung tissue and the proteome in the broncho-alveolar lavage fluid (BALF) after rat exposure by inhalation. The omics analyses were performed from 3 days up to 180 days.
2021-01-04 | PXD018900 | Pride
Project description:The immunomodulatory effects seen with exposure to multiwalled carbon nanotubes (MWCNTs) are key events in the progression to pathological outcomes. Therefore, the study of MWCNT induced immunotoxicity is crucial in determining risks posed to human health. MWCNT exposure most commonly occurs via airways, where macrophages are first line responders. Here we exploit an in vitro assay, measuring dose-dependent secretion of a wide panel of cytokines secreted from THP-1 macrophages, as a measure of immunotoxicity following the non-lethal, multi-dose exposure (IC5, IC10 and IC20) to 7 MWCNTs with different intrinsic properties. We find that an underlying tangled structure, and small aspect ratio are key properties predicting MWCNT induced immunotoxicity, mediated predominantly by IL1β cytokine secretion. To assess the mechanism of action giving rise to MWCNT immunotoxicity, a transcriptomics analysis was linked to cytokine secretion in a multilayer model established through correlation across exposure concentrations and time points. This reinforced the finding that tangled MWCNTs have greater immunomodulatory potency, displaying enrichment of immune system, signal transduction and pattern recognition associated pathways. Together our results further elucidate how structure, length and aspect ratio; critical intrinsic properties of MWCNTs, are tied to immunotoxicity.
2023-12-09 | GSE220646 | 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.
2015-08-20 | GSE60798 | 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.
2015-08-20 | GSE60800 | 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.
2015-08-20 | GSE60799 | GEO