Carcinogenesis Advance Access published online on January 3, 2008
Carcinogenesis, doi:10.1093/carcin/bgm243
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Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells
1 Université catholique de Louvain, Unité de toxicologie industrielle et médecine du travail, Avenue Mounier, 53.02; 1200 Bruxelles, Belgium
2 Vrije Universiteit Brussel, Laboratorium voor Cellulaire Genetica, Pleinlaan 2, 1050 Brussel, Belgium
3 Katholieke Universiteit Leuven, Laboratorium voor Pneumologie, Eenheid Longtoxicologie, Herestraat 49, 3000 Leuven, Belgium
4 Katholieke Universiteit Leuven, Centrum voor Oppervlaktechemie en Katalyse, Kasteelpark Arenberg 23, 3001 Heverlee, Belgium
Corresponding author : Julie Muller, Université catholique de Louvain, Unité de Toxicologie Industrielle et de Médecine du Travail, Avenue Mounier 53.02, B-1200 Bruxelles, Belgium, Tel : +32 2 764 53 36, Fax : +32 2 764 53 38, E-mail : julie.muller{at}uclouvain.be
Information on the toxicity of carbon nanotubes (CNT) 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 (RLE) exposed in vitro to MWCNT (10, 25, 50 µg/ml). Finally, we applied a human pancentromeric fluorescent probe (Fluorescent In Situ Hybridisation, FISH 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 (about a 2-fold increase at the highest dose). In vitro, we observed a significant increase of micronuclei in epithelial cells after exposure to MWCNT (up to a 2-fold increase at the cytotoxic dose of 50 µg/ml). Finally, we found that MWCNT induced both centromere-positive and negative micronuclei in MCF-7 cells. Overall, this study provides the first evidence of the potential of MWCNT to induce clastogenic as well as aneugenic events.
Received May 23, 2007; revised October 25, 2007; accepted October 26, 2007.