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.
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.
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.
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.
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.
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 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). Lung tissues were harvested 24 h, 3 d and 28 d after exposure.
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.
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.