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Int. J. Mol. Sci. 2015, 16(2), 3474-3492; doi:10.3390/ijms16023474

Comprehensive DNA Adduct Analysis Reveals Pulmonary Inflammatory Response Contributes to Genotoxic Action of Magnetite Nanoparticles

1
Division of Carcinogenesis and Prevention, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan
2
Division of Cancer Genomics, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan
3
Division of Materials Science and Engineering, Graduate School of Engineering, Yokohama National University, Hodogaya-ku, Yokohama 240-8501, Japan
4
Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, 52-1, Yada, Shizuoka 422-8526, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: James C. Bonner
Received: 11 October 2014 / Revised: 6 January 2015 / Accepted: 30 January 2015 / Published: 4 February 2015
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
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Abstract

Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields; however, its toxicological properties are not well documented. In our previous report, MGT showed genotoxicity in both in vitro and in vivo assay systems, and it was suggested that inflammatory responses exist behind the genotoxicity. To further clarify mechanisms underlying the genotoxicity, a comprehensive DNA adduct (DNA adductome) analysis was conducted using DNA samples derived from the lungs of mice exposed to MGT. In total, 30 and 42 types of DNA adducts were detected in the vehicle control and MGT-treated groups, respectively. Principal component analysis (PCA) against a subset of DNA adducts was applied and several adducts, which are deduced to be formed by inflammation or oxidative stress, as the case of etheno-deoxycytidine (εdC), revealed higher contributions to MGT exposure. By quantitative-LC-MS/MS analysis, εdC levels were significantly higher in MGT-treated mice than those of the vehicle control. Taken together with our previous data, it is suggested that inflammatory responses might be involved in the genotoxicity induced by MGT in the lungs of mice. View Full-Text
Keywords: magnetite nanoparticle; pulmonary inflammation; intratracheal instillation; DNA adductome magnetite nanoparticle; pulmonary inflammation; intratracheal instillation; DNA adductome
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ishino, K.; Kato, T.; Kato, M.; Shibata, T.; Watanabe, M.; Wakabayashi, K.; Nakagama, H.; Totsuka, Y. Comprehensive DNA Adduct Analysis Reveals Pulmonary Inflammatory Response Contributes to Genotoxic Action of Magnetite Nanoparticles. Int. J. Mol. Sci. 2015, 16, 3474-3492.

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