Related resources
Full-text held externally
Search for item elsewhere
University researcher(s)
Academic department(s)
Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis
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; Kostarelos, Kostas; Miyata, Yasumitsu; Shinohara, Hisanori; Toyokuni, Shinya
Proceedings of the National Academy of Sciences of the United States of America. 2011;108(49):E1330-E1338.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:
Full-text held externally
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 similar to 50 nm) with high crystallinity showed mesothelial cell membrane piercing and cytotoxicity in vitro and subsequent inflammo-genicity and mesotheliomagenicity in vivo. In contrast, thick (diameter similar to 150 nm) or tangled (diameter similar to 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.
Bibliographic metadata
- 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
- Kostarelos, Kostas
- Miyata, Yasumitsu
- Shinohara, Hisanori
- Toyokuni, Shinya
- Related website <Go to ISI>://WOS:000297683800010
- Times Cited: 41 Toyokuni, Shinya/C-1358-2010; Yamashita, Yoriko/B-9810-2011; Miyata, Yasumitsu/A-6246-2011; Okazaki, Yasumasa/E-7895-2010; Akatsuka, Shinya/C-9806-2010; Nagai, Hirotaka/C-9713-2010 Toyokuni, Shinya/0000-0002-5757-1109; Nagai, Hirotaka/0000-0003-0983-8670 0 41