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Multiwalled carbon nanotube-induced blood genomic changes following aspiration exposure in mice: A 1-year postexposure study.

ABSTRACT: Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to perform genome-wide mRNA profiling in mice blood to identify non-invasive blood based biomarkers for medical and occupational surveillance. The pathological results in this 1-year MWCNT post-exposure study was previously published in Snyder-Talkington et al. J Toxicol Environ Health A. 2016;79(8):352-66. doi: 10.1080/15287394.2016.1159635. Epub 2016 Apr 19. PMID: 27092743

OTHER RELATED OMICS DATASETS IN: PRJNA448940

ORGANISM(S): Mus musculus

PROVIDER: GSE126959 | GEO | 2019/07/26

REPOSITORIES: GEO

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Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study.

Project description:Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 µg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration, lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 mo, 6 mo, and 1 yr postexposure. Further, a 120-µg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all three postexposure times. Asbestos exposure elevated LDH activity at all 3 postexposure times and PMN infiltration at 1 mo and 6 mo postexposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 µg MWCNT and in asbestos-exposed mice at 1 yr postexposure. To determine potential signaling pathways involved with MWCNT-associated pathological changes in comparison to asbestos, up- and down-regulated gene expression was determined in lung tissue at 1 yr postexposure. Exposure to MWCNT tended to favor those pathways involved in immune responses, specifically T-cell responses, whereas exposure to asbestos tended to favor pathways involved in oxygen species production, electron transport, and cancer. Data indicate that MWCNT are biopersistent in the lung and induce inflammatory and fibrotic pathological alterations similar to those of crocidolite asbestos, but may reach these endpoints by different mechanisms.

2018-04-06 | GSE112780 | GEO

Transcriptomic analysis of mouse lung tissue exposed to multiwalled carbon nanotubes (Mitsui7)

Project description:There is great interest in substituting animal with in vitro experimentation in human health risk assessment, but there are rather few comparisons of in vitro and in vivo biological responses to engineered nanomaterials (ENM). We used high-content genomics tools, to compare in vivo pulmonary responses of multiwalled carbon nanotubes (MWCNT) to those in vitro in cultured lung epithelial cells at the global transcriptomic level. Mice were exposed via a single intratracheal instillation to 18, 54 or 162 ?g of Mitsui7 and samples were collected at 24 hours post-instillation. This experiment examined the pulmonary transcriptional response of female C57BL/6 mice exposed to Mitsui7 multiwalled carbon nanotubes at three doses: D1 (18 ?g), D2 (54 ?g), D3 (162 ?g), and vehicle control. Each dose group was examined 24 hours post-exposure. Each dose group had 6 biological replicates. There were a total of 22 samples included in the final analysis using a two-color reference design.

2015-05-05 | E-GEOD-46998 | biostudies-arrayexpress

Transcriptomic analysis of cultured lung epithelial cells exposed to multiwalled carbon nanotubes (Mitsui7)

Project description:There is great interest in substituting animal with in vitro experimentation in human health risk assessment, but there are rather few comparisons of in vitro and in vivo biological responses to engineered nanomaterials (ENM). We used high-content genomics tools, to compare in vivo pulmonary responses of multiwalled carbon nanotubes (MWCNT) to those in vitro in cultured lung epithelial cells at the global transcriptomic level. Mouse lung epithelial cells were incubated with 12.5, 25 and 100 μg/ml of Mitsui7 and harvested at 24 hours post-exposure. This experiment examined the mouse lung epithelial cell line FE1's response following exposure to Mitsui7 multiwalled carbon nanotubes at three doses: D1 (12.5 μg/ml), D2 (25 μg/ml), D3 (100 μg/ml), and vehicle control. Each dose group was examined 24 hours post-exposure. Each dose group had 6 biological replicates. There were a total of 22 samples included in the final analysis using a two-color reference design.

2015-05-05 | E-GEOD-46999 | biostudies-arrayexpress

Transcriptomic analysis of cultured lung epithelial cells exposed to multiwalled carbon nanotubes (Mitsui7)

2015-05-05 | GSE46999 | GEO

Transcriptomic analysis of mouse lung tissue exposed to multiwalled carbon nanotubes (Mitsui7)

2015-05-05 | GSE46998 | GEO

In vivo pulmonary genotoxicity of multiwalled-carbon nanotubes

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

Time-course of transcriptomic change in the lungs of F344 rats repeatedly exposed to a multiwalled carbon nanotube in a 2-year test

Project description:Despite intensive toxicological studies of carbon nanotubes (CNTs) over the last two decades, only a few studies have demonstrated their pulmonary carcinogenicities in chronic animal experiments, and the underlying molecular mechanisms are still unclear. To obtain molecular insights into CNT-induced lung carcinogenicity, we performed a transcriptomic analysis using a set of lung tissues collected from rats in a 2-year study, in which lung tumors were induced by repeated intratracheal instillations of a multiwalled carbon nanotube, MWNT-7. The RNA-seq-based transcriptome identified a large number of significantly differentially expressed genes at Year 0.5, Year 1, and Year 2. Ingenuity Pathway Analysis revealed that macrophage-elicited signaling pathways such as phagocytosis, acute phase response, and Toll-like receptor signaling were activated throughout the experimental period. At Year 2, cancer-related pathways including ERBB signaling and some axonal guidance signaling pathways such as EphB4 signaling were perturbed. qRT-PCR and immunohistochemistry indicated that several key molecules such as Osteopontin/Spp1, Hmox1, Mmp12, and ERBB2 were markedly altered and/or localized in the preneoplastic lesions, suggesting their participation in the induction of lung cancer. Our findings support a scenario of inflammation-induced carcinogenesis and contribute to a better understanding of the molecular mechanism of MWCNT carcinogenicity.

2023-07-17 | GSE234151 | GEO

Multiwalled carbon nanotube-induced blood genomic changes following aspiration exposure in mice: A 1-year postexposure study.

Project description:Multiwalled carbon nanotube-induced blood genomic changes following aspiration exposure in mice: A 1-year postexposure study.

| PRJNA523853 | ENA

Lung response to multi-walled carbon nanotube exposure in rats.

Project description:The projected increase in the production and use of nanomaterials is expected to result in a corresponding increase in human exposure, potentially resulting in significant morbidity and mortality. Currently, the lung toxicity of multi-walled carbon nanotubes (MWCNT), a prototype nanomaterial, was investigated in a rat model. The rats were exposed by whole-body inhalation to air (controls) or MWCNT (6 hours/day, 3 days) to result in cumulative doses of 180, 90, 45, 22.5, or 11.25 mg/m3. Lung toxicity and gene expression profiles were determined in the lungs of the control and MWCNT exposed rats one day following termination of the exposures. Moderate lung histological changes, indicative of toxicity, were detected in rats exposed to MWCNT at doses > 45 mg/m3. Changes in toxicity parameters including, lactate dehydrogenase (LDH) activity, oxidant production, cell counts of phagocytes, and cytokine levels were detected in the bronchoalveolar lavage of rats exposed to > 22.5 mg/m3 MWCNT, compared with the air controls. Lung gene expression profiling detected differences in transcript levels (fold change >1.5 and FDR p<0.05) of several genes in the rats exposed to >22.5 mg/m3 MWCNT, compared with the controls. The changes in lung toxicity and gene expression profiles exhibited a dose-response to the MWCNT administered in the rats.

2022-12-31 | GSE148869 | GEO

Expression profiling of mice exposed to multiwalled carbon nanotubes

Project description:Mice were aspirated with multiwalled carbon nanotubes in four doses ranging from 10 µg to 80 µg, plus control, and sacrificed after 1, 7, 28, and 56 days. RNA was extracted from the lungs and expression profilling by microarray was performed. This is a reference design two-color experiment. Each array was hybridized with RNA extracted from mouse lung labeled with Cy3, and universal reference RNA labeled with Cy5. Five different doses (0, 10ug, 20ug, 40ug, and 80ug) of multiwalled carbon nanotube aspiration were used and mice were sacrificed after 1, 7, 28, and 56 days. Eight replicates were used at each time/dose condition for a total of 160 arrays.

2012-06-25 | E-GEOD-29042 | biostudies-arrayexpress

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