(540g) Neoplastic-Like Transformation Ability of Carbon Nanotubes On Small Airway Epithelial Cells: Linking Toxicogenomic Signatures and Lung Cancer Hallmarks

Concern for increased risk of CNT-associated lung carcinogenesis has been raised due to asbestos-like high aspect ratio, deep pulmonary deposition, and biopersistance.  Studies evaluating long-term human health risks associated with chronic pulmonary CNT exposures compared to other well-characterized particulates (e.g. asbestos) are lacking. To address this knowledge gap, we conducted subchronic in vitro exposures of dispersed single walled CNT (D-SWCNT), multi-walled CNT (D-MWCNT) and crocidolite asbestos (ASB) to human small airway epithelial cells (SAEC) to assess their neoplastic transformation potential, an early marker of carcinogenesis. Ultrafine carbon black (D-UFCB) and dispersant-only exposed cells (DISP) served as negative controls. SAEC were exposed for 25 weeks to 0.02 µg/cm² and evaluated for morphological transformation, cancer cell phenotype and subjected to whole genome expression signature profiling.  Subchronic in vitro exposure to D-SWCNT and D-MWCNT resulted in a more aggressive neoplastic-like transformation phenotype of exposed SAECs compared to asbestos.  Furthermore, genome expression signature analysis identified oncogene signaling mechanisms in CNT-exposed SAEC that was substantially different from pro-inflammatory signaling in asbestos-exposed SAEC.  Correlation feature selection strategies identified known lung cancer markers and robust subsets of genes that could be used to develop specific gene bio-signatures for CNT-exposed cells.  In conclusion, toxicogenomic signature profiling in a CNT neoplastic-like transformed lung cell model identified particle-specific gene markers and known lung cancer markers which can potentially aid in assessing CNT exposure and detection of early disease bio-signatures.

Disclaimer: The findings and conclusions in this abstract are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.