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

• Hirotaka Nagai

  Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;

• Yasumasa Okazaki

  Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;

• Shan Hwu Chew

  Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;

• Nobuaki Misawa

  Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;

• Yoriko Yamashita

  Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;

• Shinya Akatsuka

  Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;

• Toshikazu Ishihara

  Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;

• Kyoko Yamashita

  Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;

• Yutaka Yoshikawa

  Division of Analytical and Physical Chemistry, Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan;

• Hiroyuki Yasui

  Division of Analytical and Physical Chemistry, Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan;

• Li Jiang

  Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;

• Hiroki Ohara

  Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;

• Takashi Takahashi

  Departments of dMolecular Carcinogenesis and

• Gaku Ichihara

  Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;

• Kostas Kostarelos

  Nanomedicine Laboratory, Centre for Drug Delivery Research, School of Pharmacy, University of London, London WC1N 1AX, United Kingdom; and

• Yasumitsu Miyata

  Department of Chemistry and Institute for Advanced Research, Nagoya University, Nagoya 464-8602, Japan

• Hisanori Shinohara

  Department of Chemistry and Institute for Advanced Research, Nagoya University, Nagoya 464-8602, Japan

• Shinya Toyokuni

  Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;

抄録

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.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 108 (49), E1330-, 2011-11-14

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1360565167085009024
• NII論文ID: 10030765049
• DOI: 10.1073/pnas.1110013108
• ISSN: 10916490
• ISSN: 00278424
• ISSN: http://id.crossref.org/issn/00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.1110013108
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