Whole Blood long non-coding RNA and mRNA Expression Profiles in Humans Exposed to Multi-walled Carbon Nanotubes
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE73830 | GEO | 2016/03/09
SECONDARY ACCESSION(S): PRJNA298079
REPOSITORIES: GEO
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Project description:As the application of carbon nanotubes (CNT) in consumer products continues to rise, studies have expanded to determine the associated risks of exposure on human and environmental health. In particular, several lines of evidence indicate that exposure to multi-walled carbon nanotubes (MWCNT) could pose a carcinogenic risk similar to asbestos fibers. However, to date the potential markers of MWCNT exposure are not yet explored in humans. Global mRNA and lncRNA expression profiles in the whole blood of exposed workers, having direct contact with MWCNT aerosols for atleast 6 months (n=8), were compared with expression profiles of non-exposed (n=7) workers (e.g., proffessional and/or technical staff) from the same manufacturing facility.
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Project description:Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) is established to cause local acute and chronic inflammation, fibroproliferative responses, immunotoxicity, and systemic responses in rodent studies. However, the search for representative biomarkers of exposure is an ongoing endeavor. Whole blood gene expression profiling is a promising new approach for the identification of novel disease biomarkers over more invasive methods. We asked if the whole blood transcriptome reflects pathology-specific changes in lung gene expression caused by aspiration of MWCNT. To answer this question, we performed mRNA sequencing analysis of the whole blood and lung tissue in a murine model of MWCNT bolus pharyngeal aspiration.
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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.
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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.
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