TY - JOUR T1 - An evaluation of the potential for inhaled xenobiotics to develop cancer in the lung using a 3D <em>in vitro</em> model of the human epithelial airway-wall JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p2783 AU - Martin Clift AU - Daniel Studer AU - Peter Wick AU - Thomas Geiser AU - Peter Gehr AU - Roel Schins AU - Barbara Rothen-Rutishauser Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p2783.abstract N2 - Nano-objects (NOs) produced by combustion processes, such as the content contained within diesel exhaust particles (DEPs), can potentiate cell mutagenesis leading to lung cancer. Little is understood however, regarding the potential for engineered NOs to cause genotoxicity. The aim of this project was to use an in vitro human epithelial airway-model (epithelial cell layer (16HBE14o- cells) with human monocyte derived macrophages (apical layer) and dendritic cells (basolateral layer)), with different toxicological endpoints involved in NO-induced genotoxicity. Single- and multi-walled carbon nanotubes (SWCNTs/MWCNTs), as well as crocidolite asbestos fibres (CAFs) and DEPs caused no significant (p&gt;0.05) cytotoxicity (lactate dehydrogenase release) up to 0.04mg/ml after 24hrs. Significant increases (p&lt;0.05) in both IL-8 and TNF-a levels at 0.005-0.04mg/ml over 24hrs were observed in both the apical and basolateral layers for all NOs. The NO-cell interaction (electron tomography) was only observed with macrophages and not with epithelial or dendritic cells. Initial analysis shows no changes in cell proliferation (BrdU assay) however, increased DNA damage (comet assay), possibly via an oxidant-related mechanism, in 16HBE14o- cells compared to control levels for each NO. Investigation of oxidative stress, mutagenicity and cell death endpoints are ongoing. Initial observations suggest that SWCNTs and MWCNTs may elicit genotoxicity similar to that of CAFs and DEPs via an inflammogenic/oxidant driven mechanism in vitro.We acknowledge the support of the European Respiratory Society, Fellowship LTRF-MC1572-2010 to Dr. MJD CLIFT. ER -