Next Article in Journal
Electrochemical Synthesis of Mesoporous CoPt Nanowires for Methanol Oxidation
Next Article in Special Issue
Potential Impact of Multi-Walled Carbon Nanotubes Exposure to the Seedling Stage of Selected Plant Species
Previous Article in Journal
Percolation Diffusion into Self-Assembled Mesoporous Silica Microfibres
Article Menu

Export Article

Open AccessArticle
Nanomaterials 2014, 4(1), 175-188;

Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response

Division of Cancer Development System, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan
Laboratory of Environmental Risk Evaluation, School of Life and Environmental Science, Azabu University, 1-17-71 Fuchinobe, Chuou-ku, Sagamihara, Kanagawa 252-5201, Japan
Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, Tokyo 169-0073, Japan
Department of Food and Nutritional Science, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan
Division of Materials Science and Engineering, Graduate School of Engineering, Yokohama National University, Hodogaya-ku, Yokohama 240-8501, Japan
Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, 52-1, Yada, Shizuoka 422-8526, Japan
Author to whom correspondence should be addressed.
Received: 6 January 2014 / Revised: 7 March 2014 / Accepted: 10 March 2014 / Published: 18 March 2014
(This article belongs to the Special Issue Nanotoxicology)
Full-Text   |   PDF [552 KB, uploaded 19 March 2014]   |  


Nanomaterials are useful for their characteristic properties and are commonly used in various fields. Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields, whereas their toxicological properties are not well documented. A safety assessment is thus urgently required for MGT, and genotoxicity is one of the most serious concerns. In the present study, we examined genotoxic effects of MGT using mice and revealed that DNA damage analyzed by a comet assay in the lungs of imprinting control region (ICR) mice intratracheally instilled with a single dose of 0.05 or 0.2 mg/animal of MGT was approximately two- to three-fold higher than that of vehicle-control animals. Furthermore, in gpt delta transgenic mice, gpt mutant frequency (MF) in the lungs of the group exposed to four consecutive doses of 0.2 mg MGT was significantly higher than in the control group. Mutation spectrum analysis showed that base substitutions were predominantly induced by MGT, among which G:C to A:T transition and G:C to T:A transversion were the most significant. To clarify the mechanism of mutation caused by MGT, we analyzed the formation of DNA adducts in the lungs of mice exposed to MGT. DNA was extracted from lungs of mice 3, 24, 72 and 168 h after intratracheal instillation of 0.2 mg/body of MGT, and digested enzymatically. 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and lipid peroxide-related DNA adducts were quantified by stable isotope dilution liquid chromatography-mass spectrometry (LC-MS/MS). Compared with vehicle control, these DNA adduct levels were significantly increased in the MGT-treated mice. In addition to oxidative stress- and inflammation related-DNA adduct formations, inflammatory cell infiltration and focal granulomatous formations were also observed in the lungs of MGT-treated mice. Based on these findings, it is suggested that inflammatory responses are probably involved in the genotoxicity induced by MGT in the lungs of mice. View Full-Text
Keywords: magnetite nanoparticle (MGT); pulmonary inflammation; intratracheal instillation; DNA damage; genotoxicity magnetite nanoparticle (MGT); pulmonary inflammation; intratracheal instillation; DNA damage; genotoxicity

Figure 1

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Share & Cite This Article

MDPI and ACS Style

Totsuka, Y.; Ishino, K.; Kato, T.; Goto, S.; Tada, Y.; Nakae, D.; Watanabe, M.; Wakabayashi, K. Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response. Nanomaterials 2014, 4, 175-188.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Nanomaterials EISSN 2079-4991 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top