Project description:Carbon nanotubes (CNTs) are fibrous particulates made up of elemental carbon and a novel nanomaterial known for its variety of industrial applications. It has been shown that lung exposure to CNTs may cause adverse effects inclunding lung inflammation and remodeling in experimental models. We investigated the impact of genetic background on the development of adverse outcomes by comparing several common inbred mouse strains and found that C57Bl/6 and DBA/2 strains were polarized in their sensitivity to adverse changes at 4 weeks following an exposure to 4 mg/kg CNT. Here we compare underlying gene expression profiles which may inform the understanding of lung biology underpinning genetic susceptibility to adverse outcomes following environmental or occupational exposure to CNTs.
Project description:Transcriptional profiling of mouse lung tissue comparing control vs exposure to different carbon nanotubes. The aim was to determine if the physico-chemical properties influence the genotoxic, inflammatory and pro-fibrotic responses.
Project description:Mouse strains have been identified that are resistant (i.e. DBA/2) or susceptible (i.e. C57BL/6) to infection from pathogenic fungus Coccidioides immitis. However, the genetic and immunological basis for this difference has not been fully characterized. Microarray technology was used to identify genes that were differentially expressed in lung tissue between resistant DBA/2 and sensitive C57BL/6 mice after infection with C. immitis.
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:Cap Analysis of Gene Expression (CAGE) applied on carbon nanotubes exposed lung tissue to identify alternative promoter and enhancer usage after 24 hr of exposure in order to investigate the nature of the response observed in these mice.
Project description:Mouse strains have been identified that are resistant (i.e. DBA/2) or susceptible (i.e. C57BL/6) to infection from pathogenic fungus Coccidioides immitis. However, the genetic and immunological basis for this difference has not been fully characterized. Microarray technology was used to identify genes that were differentially expressed in lung tissue between resistant DBA/2 and sensitive C57BL/6 mice after infection with C. immitis. C57BL/6 and DBA/2 mice were infected with arthoconidia of C. immitis and RNA was extracted at different days post-infection and hybridized to Affymetrix microarrays (MGU74Av2), in order to identify differentially expressed genes between the two strains.
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: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.
