Organ accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rasH2 mice
Atsushi Sobajima,1 Hisao Haniu,1,2 Hiroki Nomura,1 Manabu Tanaka,1 Takashi Takizawa,1 Takayuki Kamanaka,1 Kaoru Aoki,1,3 Masanori Okamoto,1 Kazushige Yoshida,1 Jun Sasaki,1 Kumiko Ajima,2 Chika Kuroda,1,2 Haruka Ishida,2 Satomi Okano,2 Katsuya Ueda,2 Hiroyuki Kato,1 Naoto Saito1,21Department of Orth...
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Dove Medical Press
2019
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oai:doaj.org-article:9a49f4e2940e4cd8be0ee4e7d330a7832021-12-02T09:45:00ZOrgan accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rasH2 mice1178-2013https://doaj.org/article/9a49f4e2940e4cd8be0ee4e7d330a7832019-08-01T00:00:00Zhttps://www.dovepress.com/organ-accumulation-and-carcinogenicity-of-highly-dispersed-multi-walle-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Atsushi Sobajima,1 Hisao Haniu,1,2 Hiroki Nomura,1 Manabu Tanaka,1 Takashi Takizawa,1 Takayuki Kamanaka,1 Kaoru Aoki,1,3 Masanori Okamoto,1 Kazushige Yoshida,1 Jun Sasaki,1 Kumiko Ajima,2 Chika Kuroda,1,2 Haruka Ishida,2 Satomi Okano,2 Katsuya Ueda,2 Hiroyuki Kato,1 Naoto Saito1,21Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; 2Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; 3Department of Applied Physical Therapy, Shinshu University School of Health Sciences, Matsumoto, Nagano, JapanPurpose: Multiwalled carbon nanotubes (MWCNTs) have been known to enter the circulatory system via the lungs from inhalation exposure; however, its carcinogenicity and subsequent accumulation in other organs have not been adequately reported in the literature. Moreover, the safety of MWCNTs as a biomaterial has remained a matter of debate, particularly when the material enters the circulatory system. To address these problems, we used carcinogenic rasH2 transgenic mice to intravenously administer highly dispersed MWCNTs and to evaluate their carcinogenicity and accumulation in the organs.Methods: Two types of MWCNTs (thin- and thick-MWCNTs) were intravenously administered at a high dose (approximately 0.7 mg per kg body weight) and low dose (approximately 0.07 mg per kg body weight).Results: MWCNTs showed pancreatic accumulation in 3.2% of mice administered with MWCNTs, but there was no accumulation in other organs. In addition, there was no significant difference in the incidence of tumor among the four MWCNTs-administered groups compared to the vehicle group without MWCNTs administration. Blood tests revealed elevated levels in mean red blood cell volume and mean red blood cell hemoglobin level for the MWCNTs-administered group, in addition to an increase in eotaxin.Conclusion: The present study demonstrated that the use of current technology to sufficiently disperse MWCNTs resulted in minimal organ accumulation with no evidence of carcinogenicity.Keywords: multiwalled carbon nanotubes, rasH2 transgenic mouse, carcinogenicity, organ accumulation, dispersionSobajima AHaniu HNomura HTanaka MTakizawa TKamanaka TAoki KOkamoto MYoshida KSasaki JAjima KKuroda CIshida HOkano SUeda KKato HSaito NDove Medical Pressarticlemultiwalled carbon nanotubesrasH2 transgenic mousecarcinogenicityorgan accumulationdispersionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 6465-6480 (2019) |
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multiwalled carbon nanotubes rasH2 transgenic mouse carcinogenicity organ accumulation dispersion Medicine (General) R5-920 |
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multiwalled carbon nanotubes rasH2 transgenic mouse carcinogenicity organ accumulation dispersion Medicine (General) R5-920 Sobajima A Haniu H Nomura H Tanaka M Takizawa T Kamanaka T Aoki K Okamoto M Yoshida K Sasaki J Ajima K Kuroda C Ishida H Okano S Ueda K Kato H Saito N Organ accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rasH2 mice |
| description |
Atsushi Sobajima,1 Hisao Haniu,1,2 Hiroki Nomura,1 Manabu Tanaka,1 Takashi Takizawa,1 Takayuki Kamanaka,1 Kaoru Aoki,1,3 Masanori Okamoto,1 Kazushige Yoshida,1 Jun Sasaki,1 Kumiko Ajima,2 Chika Kuroda,1,2 Haruka Ishida,2 Satomi Okano,2 Katsuya Ueda,2 Hiroyuki Kato,1 Naoto Saito1,21Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; 2Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; 3Department of Applied Physical Therapy, Shinshu University School of Health Sciences, Matsumoto, Nagano, JapanPurpose: Multiwalled carbon nanotubes (MWCNTs) have been known to enter the circulatory system via the lungs from inhalation exposure; however, its carcinogenicity and subsequent accumulation in other organs have not been adequately reported in the literature. Moreover, the safety of MWCNTs as a biomaterial has remained a matter of debate, particularly when the material enters the circulatory system. To address these problems, we used carcinogenic rasH2 transgenic mice to intravenously administer highly dispersed MWCNTs and to evaluate their carcinogenicity and accumulation in the organs.Methods: Two types of MWCNTs (thin- and thick-MWCNTs) were intravenously administered at a high dose (approximately 0.7 mg per kg body weight) and low dose (approximately 0.07 mg per kg body weight).Results: MWCNTs showed pancreatic accumulation in 3.2% of mice administered with MWCNTs, but there was no accumulation in other organs. In addition, there was no significant difference in the incidence of tumor among the four MWCNTs-administered groups compared to the vehicle group without MWCNTs administration. Blood tests revealed elevated levels in mean red blood cell volume and mean red blood cell hemoglobin level for the MWCNTs-administered group, in addition to an increase in eotaxin.Conclusion: The present study demonstrated that the use of current technology to sufficiently disperse MWCNTs resulted in minimal organ accumulation with no evidence of carcinogenicity.Keywords: multiwalled carbon nanotubes, rasH2 transgenic mouse, carcinogenicity, organ accumulation, dispersion |
| format |
article |
| author |
Sobajima A Haniu H Nomura H Tanaka M Takizawa T Kamanaka T Aoki K Okamoto M Yoshida K Sasaki J Ajima K Kuroda C Ishida H Okano S Ueda K Kato H Saito N |
| author_facet |
Sobajima A Haniu H Nomura H Tanaka M Takizawa T Kamanaka T Aoki K Okamoto M Yoshida K Sasaki J Ajima K Kuroda C Ishida H Okano S Ueda K Kato H Saito N |
| author_sort |
Sobajima A |
| title |
Organ accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rasH2 mice |
| title_short |
Organ accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rasH2 mice |
| title_full |
Organ accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rasH2 mice |
| title_fullStr |
Organ accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rasH2 mice |
| title_full_unstemmed |
Organ accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rasH2 mice |
| title_sort |
organ accumulation and carcinogenicity of highly dispersed multi-walled carbon nanotubes administered intravenously in transgenic rash2 mice |
| publisher |
Dove Medical Press |
| publishDate |
2019 |
| url |
https://doaj.org/article/9a49f4e2940e4cd8be0ee4e7d330a783 |
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