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

International Journal of Molecular Sciences

Kousuke Ishino³  Tatsuya Kato³  Mamoru Kato¹  Tatsuhiro Shibata¹  Masatoshi Watanabe²  Keiji Wakabayashi⁴  Hitoshi Nakagama³  Yukari Totsuka³ 

[1] Division of Cancer Genomics, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan; E-Mails:;Division of Materials Science and Engineering, Graduate School of Engineering, Yokohama National University, Hodogaya-ku, Yokohama 240-8501, Japan; E-Mail:;Division of Carcinogenesis and Prevention, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan; E-Mails:;Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, 52-1, Yada, Shizuoka 422-8526, Japan; E-Mail:

关键词: magnetite nanoparticle;    pulmonary inflammation;    intratracheal instillation;    DNA adductome;   

DOI  :  10.3390/ijms16023474

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.