title: Comprehensive DNA adduct analysis reveals pulmonary inflammatory response contributes to genotoxic action of magnetite nanoparticles.
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.
authors: Division of Carcinogenesis and Prevention, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. kishino@ncc.go.jp.
authors: Kousuke
authors: K
authors: Ishino
authors: Division of Carcinogenesis and Prevention, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. takatou1311@gmail.com.
authors: Tatsuya
authors: T
authors: Kato
authors: Division of Cancer Genomics, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. mamkato@ncc.go.jp.
authors: Mamoru
authors: M
authors: Kato
authors: Division of Cancer Genomics, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. tashibat@ncc.go.jp.
authors: Tatsuhiro
authors: T
authors: Shibata
authors: Division of Materials Science and Engineering, Graduate School of Engineering, Yokohama National University, Hodogaya-ku, Yokohama 240-8501, Japan. mawata@ynu.ac.jp.
authors: Masatoshi
authors: M
authors: Watanabe
authors: Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, 52-1, Yada, Shizuoka 422-8526, Japan. kwakabayashi@u-shizuoka-ken.ac.jp.
authors: Keiji
authors: K
authors: Wakabayashi
authors: Division of Carcinogenesis and Prevention, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. hnakagam@ncc.go.jp.
authors: Hitoshi
authors: H
authors: Nakagama
authors: Division of Carcinogenesis and Prevention, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. ytotsuka@ncc.go.jp.
authors: Yukari
authors: Y
authors: Totsuka
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects*; D018736:DNA Adducts / Q000032:analysis*; D004249:DNA Damage / Q000187:drug effects*; D003841:Deoxycytidine / Q000737:chemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics*; D025341:Principal Component Analysis
chemical_list: D003287:Contrast Media; D018736:DNA Adducts; D058185:Magnetite Nanoparticles; D003841:Deoxycytidine