Size- and shape-dependent pleural translocation, deposition, fibrogenesis and mesothelial proliferation by multi-walled carbon nanotubes

Cancer Science. 2014 May 11. [Epub ahead of print] [Link]

Alexander DB, Fukamachi K, Futakuchi M, Hirose A, Kanno J, Numano T, Omori T, Suzui M, Tsuda H, Xu J.

Abstract

Multi-walled carbon nanotubes (MWCNT) have a fibrous structure similar to asbestos, raising concern that MWCNT exposure may lead to asbestos-like diseases. Previously we showed that MWCNT translocated from the lung alveoli into the pleural cavity and caused mesothelial proliferation and fibrosis in the visceral pleura. MWCNTs were not found in the parietal pleura, the initial site of development of asbestos-caused pleural diseases in humans, probably due to the short exposure period of the study. In the present study, we extended the exposure period to 24 weeks to determine whether the size and shape of MWCNT impact on deposition and lesion development in the pleura and lung. Two different MWCNTs were chosen for this study: a larger sized needle-like MWCNT (MWCNT-L, l=8 μm, d=150 nm) and a smaller sized MWCNT (MWCNT-S, l=3 μm, d=15 nm), which forms cotton candy-like aggregates. MWCNT-L and MWCNT-S suspensions were administrated to the rat lung once every two weeks for 24 weeks by trans-tracheal intra-pulmonary spraying. MWCNT-L, but not MWCNT-S, was found to translocate into the pleural cavity, deposit in the parietal pleura and induce fibrosis and patchy parietal mesothelial proliferation lesions. MWCNT-L also induced stronger inflammatory reactions including increased inflammatory cell number and cytokine/chemokine levels in the pleural cavity lavage than MWCNT-S. In contrast, MWCNT-S induced stronger inflammation and higher 8-OHdG level in the lung tissue than MWCNT-L. These results suggest that MWCNT-L has higher risk of causing asbestos-like pleural lesions releveant to mesothelioma development. This article is protected by copyright. All rights reserved.