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Genotoxicity of nano/microparticles in in vitro micronuclei, in vivo comet and mutation assay systems |
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| Authors: | Yukari Totsuka Takashi Higuchi Toshio Imai Akiyoshi Nishikawa Takehiko Nohmi Tatsuya Kato Shuich Masuda Naohide Kinae Kyoko Hiyoshi Sayaka Ogo Masanobu Kawanishi Takashi Yagi Takamichi Ichinose Nobutaka Fukumori Masatoshi Watanabe Takashi Sugimura Keiji Wakabayashi |
| Affiliation: | 1. Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045, Japan 2. Central Animal Laboratory, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045, Japan 3. Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan 4. Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan 5. Department of Food and Nutritional Sciences, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1, Yada, Shizuoka, 422-8526, Japan 6. Fundamental Nursing, School of Nursing, University of Shizuoka, 52-1, Yada, Shizuoka, 422-8526, Japan 7. Environmental Genetics Laboratory, Frontier Science Innovation Center, Osaka Prefecture University, 1-2 Gakuen-cho Naka-ku, Sakai-city, Osaka, 599-8570, Japan 8. Department of Health Sciences, Oita University of Nursing and Health Sciences, 2944-9 Megusuno, Oita-city, Oita, Japan 9. Department of Environmental Health and Toxicology, Tokyo Metropolitan Institute of Public Health, 24-1, Hyakunin-cho 3-Chome, Shinjuku-ku, Tokyo, 169-0073, Japan 10. Division of Materials Science and Engineering, Yokohama National University, Graduate School of Engineering, 79-5, Tokiwadai, Hodogaya-ku, Yokohama, 240-8501, Japan |
| Abstract: | BackgroundRecently, manufactured nano/microparticles such as fullerenes (C60), carbon black (CB) and ceramic fiber are being widely used because of their desirable properties in industrial, medical and cosmetic fields. However, there are few data on these particles in mammalian mutagenesis and carcinogenesis. To examine genotoxic effects by C60, CB and kaolin, an in vitro micronuclei (MN) test was conducted with human lung cancer cell line, A549 cells. In addition, DNA damage and mutations were analyzed by in vivo assay systems using male C57BL/6J or gpt delta transgenic mice which were intratracheally instilled with single or multiple doses of 0.2 mg per animal of particles.ResultsIn in vitro genotoxic analysis, increased MN frequencies were observed in A549 cells treated with C60, CB and kaolin in a dose-dependent manner. These three nano/microparticles also induced DNA damage in the lungs of C57BL/6J mice measured by comet assay. Moreover, single or multiple instillations of C60 and kaolin, increased either or both of gpt and Spi- mutant frequencies in the lungs of gpt delta transgenic mice. Mutation spectra analysis showed transversions were predominant, and more than 60% of the base substitutions occurred at G:C base pairs in the gpt genes. The G:C to C:G transversion was commonly increased by these particle instillations.ConclusionManufactured nano/microparticles, CB, C60 and kaolin, were shown to be genotoxic in in vitro and in vivo assay systems. |
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