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

Content Provider	PubMed Central
Author	Nagai, Hirotaka Okazaki, Yasumasa Chew, Shan Hwu Misawa, Nobuaki Yamashita, Yoriko Akatsuka, Shinya Ishihara, Toshikazu Yamashita, Kyoko Yoshikawa, Yutaka Yasui, Hiroyuki Jiang, Li Ohara, Hiroki Takahashi, Takashi Ichihara, Gaku Kostas, Kostarelos Miyata, Yasumitsu Shinohara, Hisanori Toyokuni, Shinya
Abstract	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.
Related Links	http://dx.doi.org/10.1073/pnas.1110013108
Starting Page	1330
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	49
Volume Number	108
Language	English
Publisher	National Academy of Sciences
Publisher Date	2011-12-06
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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