Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis

Nagai, H., Okazaki, Y., Chew, S.H., Misawa, N., Yamashita, Y., Akatsuka, S., Ishihara, T., Yamashita, K., Yoshikawa, Y., Yasui, H., Jiang, L., Ohara, H., Takahashi, T., Ichihara, G., Kostarelos, K., Miyata, Y., Shinohara, H. and Toyokuni, S. (2011) Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis. Proceedings of the National Academy of Sciences, 108 (49). E1330-E1338. 10.1073/pnas.1110013108.

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Official URL: http://www.pnas.org.libproxy.ucl.ac.uk/content/108/49/E1330.full.pdf+html

DOI: 10.1073/pnas.1110013108


Multiwalled carbon nanotubes (MWCNTs) have the potential for widespread applications in engineering and materials science. However, because of their needle-like shape and high durability, concerns have been raised that MWCNTs may induce asbestos-like pathogenicity. Although recent studies have demonstrated that MWCNTs induce various types of reactivities, the physicochemical features of MWCNTs that determine their cytotoxicity and carcinogenicity in mesothelial cells remain unclear. Here, we showed that the deleterious effects of nonfunctionalized MWCNTs on human mesothelial cells were associated with their diameter-dependent piercing of the cell membrane. Thin MWCNTs (diameter ∼ 50 nm) with high crystallinity showed mesothelial cell membrane piercing and cytotoxicity in vitro and subsequent inflammogenicity and mesotheliomagenicity in vivo. In contrast, thick (diameter ∼ 150 nm) or tangled (diameter ∼ 2-20 nm) MWCNTs were less toxic, inflammogenic, and carcinogenic. Thin and thick MWCNTs similarly affected macrophages. Mesotheliomas induced by MWCNTs shared homozygous deletion of Cdkn2a/2b tumor suppressor genes, similar to mesotheliomas induced by asbestos. Thus, we propose that different degrees of direct mesothelial injury by thin and thick MWCNTs are responsible for the extent of inflammogenicity and carcinogenicity. This work suggests that control of the diameter of MWCNTs could reduce the potential hazard to human health.

Item Type:Article
Uncontrolled Keywords:Environmental health; Inflammation; Nanotoxicology
Departments, units and centres:Department of Pharmaceutics > Department of Pharmaceutics
ID Code:2802
Journal or Publication Title:Proceedings of the National Academy of Sciences
Deposited By:Library Staff
Deposited On:10 Feb 2012 11:57
Last Modified:24 Feb 2012 09:33

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