Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells.

Information on the toxicity of carbon nanotubes is still fragmentary but indicates that these particles can induce adverse effects. We previously demonstrated in rats that, when purified multi-wall carbon nanotubes (MWCNT) reach the lung, they are biopersistent and induce lung inflammation as well as fibrosis. The present study was designed to address the genotoxic potential of this material in the same species. In vivo, micronuclei (MN) were assessed in type II pneumocytes 3 days after a single intra-tracheal administration of MWCNT (0.5 or 2 mg). We also used the cytokinesis-block micronucleus assay in rat lung epithelial cells exposed in vitro to MWCNT (10, 25, 50 mug/ml). Finally, we applied a human pancentromeric fluorescent probe (fluorescent in situ hybridization assay) to differentiate clastogenic and/or aneugenic mechanisms in a human epithelial cell line (MCF-7). In vivo, we found a significant and dose-dependent increase in micronucleated pneumocytes after a single administration of MWCNT ( approximately a 2-fold increase at the highest dose). In vitro, we observed a significant increase of MN in epithelial cells after exposure to MWCNT (up to a 2-fold increase at the cytotoxic dose of 50 mug/ml). Finally, we found that MWCNT induced both centromere-positive and -negative MN in MCF-7 cells. Overall, this study provides the first evidence of the potential of MWCNT to induce clastogenic as well as aneugenic events.