Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression data of primary human bronchial epithelial cells exposed to crocidolite asbestos and cristobalite silica mineral dusts

ABSTRACT: Gene expression microarrays were used to compare gene alterations induced by exposure to equitoxic doses of crocidolite asbestos and cristobalite silica in an isolate of normal human bronchial epithelial cells. Primary human bronchial epithelial cells (NHBE) were exposed to crocidolite asbestos, cristobalite silica, and saline as control for 24 hours. Total RNA was extracted from cell cultures, 3 separate cultures were used for each condition. The isolated RNA was used to analyze mRNA expression via Affymetix GeneChip Human U133A 2.0 arrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Paul Peeters

PROVIDER: E-GEOD-62769 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Human mesothelial cells (LP9/TERT-1) were exposed to low and high (15 and 75 μm2/cm2 dish) equal surface area concentrations of crocidolite asbestos, nonfibrous talc, fine titanium dioxide (TiO2), or glass beads for 8 or 24 h. RNA was then isolated for Affymetrix microarrays, GeneSifter analysis and QRT-PCR. Gene changes by asbestos were concentration- and time-dependent. At low nontoxic concentrations, asbestos caused significant changes in mRNA expression of 29 genes at 8 h and 205 genes at 24 h, whereas changes in mRNA levels of 236 genes occurred in cells exposed to high concentrations of asbestos for 8 h. Human primary pleural mesothelial cells also showed the same patterns of increased gene expression by asbestos. Nonfibrous talc at low concentrations in LP9/TERT-1 mesothelial cells caused increased expression of 1 gene Activating Transcription Factor 3 (ATF3) at 8 h and no changes at 24 h, whereas expression levels of 30 genes were elevated at 8 h at high talc concentrations. Fine TiO2 or glass beads caused no changes in gene expression. In human ovarian epithelial (IOSE) cells, asbestos at high concentrations elevated expression of 2 genes (NR4A2, MIP2) at 8 h and 16 genes at 24 h that were distinct from those elevated in mesothelial cells. Since ATF3 was the most highly expressed gene by asbestos, its functional importance in cytokine production by LP9/TERT-1 cells was assessed using siRNA approaches. Results reveal that ATF3 modulates production of inflammatory cytokines (IL-1β, IL-13, G-CSF) and growth factors (VEGF and PDGF-BB) in human mesothelial cells. Microarrays were performed on samples from 3 independent experiments. All cell types, time points, and mineral types and concentrations were included in all 3 experiments. For each experiment, n=3 dishes were pooled into one sample per treatment group. Each of the pooled samples was analyzed on a separate array, i.e., n=3 arrays per condition (3 independent biological replicates). We tested the hypothesis that alteration in gene expression in human cells correlate with mineral pathogenicity. We used GeneSifter program to analyze our data and pairwise analysis showed that number of gene changes correlate with toxicity of pathogenic minerals. While non-pathogenic minerals glass beads and fine TiO2 treatment to cell resulted in no gene change, crocidolite asbestos caused maximum number of gene changes followed by talc.

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.

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Gene expression data of primary human bronchial epithelial cells exposed to crocidolite asbestos and cristobalite silica mineral dusts

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