Multi-walled carbon nanotube-induced gene expression in vitro
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PROVIDER: PRJNA532386 | ENA |
REPOSITORIES: ENA
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Project description:There is a current interest in reducing the in vivo toxicity testing of nanomaterials in animals by increasing toxicity testing using in vitro cellular assays; however, toxicological results are seldom concordant between in vivo and in vitro models. This study compared global multi-walled carbon nanotube (MWCNT)-induced gene expression from human lung epithelial and microvascular endothelial cells in monoculture and coculture with gene expression from mouse lungs exposed to MWCNT. Using a cutoff of 10% false discovery rate and 1.5 fold change, we determined that there were more concordant genes (gene expression both up- or downregulated in vivo and in vitro) expressed in both cell types in coculture than in monoculture. When reduced to only those genes involved in inflammation and fibrosis, known outcomes of in vivo MWCNT exposure, there were more disease-related concordant genes expressed in coculture than monoculture. Additionally, different cellular signaling pathways are activated in response to MWCNT dependent upon culturing conditions. As coculture gene expression better correlated with in vivo gene expression, we suggest that cellular cocultures may offer enhanced in vitro models for nanoparticle risk assessment and the reduction of in vivo toxicological testing.
2019-04-12 | GSE129640 | GEO
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:Lung response to multi-walled carbon nanotube exposure in rats.
| PRJNA625993 | ENA
Project description:Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis
| PRJNA611721 | ENA
Project description:Recent in vivo studies reported that inhaled carbon nanotube distribute in the alveolar region resulting in an acute inflammation, progressive fibrotic response and particle accumulation at the bronchoalveolar junction with low clearance. With similar biopersistence and shape as asbestos, a known lung carcinogen, growing concern has arisen for elevated risk of carbon nanotube-induced lung carcinogenesis; however few studies have evaluated long-term human health risks associated with chronic pulmonary carbon nanotube exposures compared to asbestos. To address this knowledge gap, we conducted subchronic in vitro exposures of dispersed single walled carbon nanotube, multi-walled carbon nanotube and crocidolite asbestos to human small airway epithelial cells to assess their neoplastic transformation potential. Subchronic single-, multi-walled carbon nanotube and asbestos exposures caused human lung cell neoplastic transformation exhibited by increased proliferation, anchorage-independent growth, invasion and angiogenesis. Whole genome profiling and protein expression analyses showed that carbon nanotube-induced transformation mechanism(s) was largely different from asbestos-related inflammatory signaling, suggesting specific carbon nanotube-induced carcinogenic potential. This study provides novel carbon nanotube and asbestos toxicogenomic information for risk assessment and an in vitro model to evaluate transformation potential of carbon nanotubes and other nanoparticles.
2013-07-22 | GSE41178 | GEO
Project description:Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis [methylation]
| PRJNA611710 | ENA
Project description:Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis [expression]
| PRJNA611724 | ENA
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
Project description:Recent in vivo studies reported that inhaled carbon nanotube distribute in the alveolar region resulting in an acute inflammation, progressive fibrotic response and particle accumulation at the bronchoalveolar junction with low clearance. With similar biopersistence and shape as asbestos, a known lung carcinogen, growing concern has arisen for elevated risk of carbon nanotube-induced lung carcinogenesis; however few studies have evaluated long-term human health risks associated with chronic pulmonary carbon nanotube exposures compared to asbestos. To address this knowledge gap, we conducted subchronic in vitro exposures of dispersed single walled carbon nanotube, multi-walled carbon nanotube and crocidolite asbestos to human small airway epithelial cells to assess their neoplastic transformation potential. Subchronic single-, multi-walled carbon nanotube and asbestos exposures caused human lung cell neoplastic transformation exhibited by increased proliferation, anchorage-independent growth, invasion and angiogenesis. Whole genome profiling and protein expression analyses showed that carbon nanotube-induced transformation mechanism(s) was largely different from asbestos-related inflammatory signaling, suggesting specific carbon nanotube-induced carcinogenic potential. This study provides novel carbon nanotube and asbestos toxicogenomic information for risk assessment and an in vitro model to evaluate transformation potential of carbon nanotubes and other nanoparticles. Whole genome expression profiling was conducted on human immortalized small airway epithelial cells (SAEC-hTERT) following 6 month in vitro chronic exposure to six separate treatments to assess differences in carbon nanotube (CNT) vs. asbestos potential tumorigenesis signaling. Dispersed single wall CNT (D-SWCNT), multi-wall CNT (D-MWCNT), ultrafine carbon black (D-UFCB), crocidolite asbestos (ASB) and saline (SAL) exposed cells were compared to SurvantaM-BM-. dispersant (DISP) passage control cells. Each treatment possessed 3 biological cDNA replicates. One technical replicate was performed per biological sample.
2013-07-22 | E-GEOD-41178 | biostudies-arrayexpress
Project description:To evaluate the biological effects at the transcriptional level of manufactured nanomaterials, we performed whole genome microarrays of rat alveolar macrophages (NR8383) exposed to multi-walled carbon nanotubes (MWCNTs) with different physicochemical properties.
2019-09-07 | GSE137008 | GEO