Phenotypic anchoring of subchronic carbon nanotube and asbestos exposure to small airway epithelial cells: linking toxicogenomic and neoplastic transformation responses.
Stueckle-TA; Mishra-A; Derk-R; Meighan-T; Castranova-V; Rojanasakul-Y; Wang-L
Toxicologist 2012 Mar; 126(Suppl 1):272-273
Recent studies reported that inhaled carbon nanotube (CNT) exposure results in elevated risk for rapid interstitial fibrosis and persistence within exposed tissues. To our knowledge, no study has yet evaluated long-term human health risks associated with chronic pulmonary CNT exposures compared to asbestos, a known lung carcinogen with similar shape. To address this knowledge gap, we conducted subchronic in vitro exposures of dispersed single-walled CNT (D-SWCNT), multiwalled CNT (D-MWCNT) and crocidolite asbestos (ASB) to human small airway epithelial cells (SAEC). Ultrafine carbon black (D-UFCB) and dispersant-only exposed cells (DISP) served as negative controls. SAEC were exposed for 25 weeks to 0.02 microg/cm2 and evaluated for cancer cell phenotype. Next, mRNA samples were subjected to whole genome microarray and rtPCR analyses for toxicogenomic evaluation. Differentially expressed genes were uploaded to Ingenuity Pathway Analysis to identify novel mechanisms promoting neoplastic transformation. Both DSWCNT and D-MWCNT-treated cells exhibited increased proliferation, invasion, anchorage-independent cell growth and angiogenesis compared to other treatments. Hierarchical cluster analysis revealed that D-SWCNT and D-MWCNT cells shared the most similar genome expression profile while ASB, D-UFCB and DISP cells expressed dissimilar genome profiles. Both D-SWCNT and DMWCNT cells expressed significant changes in genes associated with cell death, movement, proliferation and cancer. Top ranked pathway along with western blot analyses identified several altered signaling pathways and transcription factors associated with oncogenesis. Phenotypic anchoring of toxicogenomic response to neoplastic cell transformation following in vitro subchronic nanomaterial exposure can potentially serve to identify novel mechanisms of action and provide human health risk assessment data.
Nanotechnology; Toxic-materials; Health-hazards; Immune-reaction; Immune-system; Cell-function; Pulmonary-clearance; Cellular-uptake; Toxic-effects; Respiratory-system-disorders; Pulmonary-system-disorders; Lung-cells; Lung-disorders; Lung-function; Lung-tissue; Particulates; In-vitro-study; Exposure-assessment; Exposure-methods; Inhalation-studies; Risk-analysis; Risk-factors; Long-term-study; Genotoxic-effects; Asbestos-fibers; Cell-growth; Genes; Cancer; Neoplasms; Oncogenesis; Cell-transformation; Cell-alteration
7440-44-0; 1332-21-4; 12001-28-4; 1333-86-4
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California