Unknown,Transcriptomics,Genomics,Proteomics

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Changes in cholesterol homeostasis and acute phase response following pulmonary exposure to multi-walled carbon nanotubes links carbon nanotube exposure to risk of cardiovascular disease

ABSTRACT: 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-

ORGANISM(S): Mus musculus

SUBMITTER: Sarah Poulsen

PROVIDER: E-GEOD-61366 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease.

Poulsen Sarah S SS Saber Anne T AT Mortensen Alicja A Szarek Józef J Wu Dongmei D Williams Andrew A Andersen Ole O Jacobsen Nicklas R NR Yauk Carole L CL Yauk Carole L CL Wallin Håkan H Halappanavar Sabina S Vogel Ulla U

Toxicology and applied pharmacology 20150122 3

Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma ...[more]

PMID: 25620056

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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.

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.

Dataset Information

Changes in cholesterol homeostasis and acute phase response following pulmonary exposure to multi-walled carbon nanotubes links carbon nanotube exposure to risk of cardiovascular disease

Publications

Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease.

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