In Vitro and In Vivo Genotoxicity Induced by Fullerene (C60) and Kaolin

  • Totsuka Yukari
    Division of Cancer Development System, National Cancer Center Research Institute
  • Kato Tatsuya
    Division of Cancer Development System, National Cancer Center Research Institute Department of Food & Nutritional Science, Graduate School of Nutrition & Environmental Science, University of Shizuoka
  • Masuda Shu-ichi
    Department of Food & Nutritional Science, Graduate School of Nutrition & Environmental Science, University of Shizuoka
  • Ishino Kousuke
    Division of Cancer Development System, National Cancer Center Research Institute
  • Matsumoto Yoko
    Division of Cancer Development System, National Cancer Center Research Institute Laboratory of Environmental Risk Evaluation, School of Life and Enviromental Science, Azabu University
  • Goto Sumio
    Laboratory of Environmental Risk Evaluation, School of Life and Enviromental Science, Azabu University
  • Kawanishi Masanobu
    Environmental Genetics Laboratory, Frontier Science Innovation Center, Osaka Prefecture University
  • Yagi Takashi
    Environmental Genetics Laboratory, Frontier Science Innovation Center, Osaka Prefecture University
  • Wakabayashi Keiji
    Department of Food & Nutritional Science, Graduate School of Nutrition & Environmental Science, University of Shizuoka

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Nanomaterials are being utilized for many kinds of industrial products, and the assessment of genotoxicity and safety of nanomaterials is therefore of concern. In the present study, we examined the genotoxic effects of fullerene (C60) and kaolin using in vitro and in vivo genotoxicity systems. Both nanomaterials significantly induced micronuclei and enhanced frequency of sister chromatid exchange (SCE) in cultured mammalian cells. When ICR mice were intratracheally instilled with these nanomaterials, DNA damage of the lungs increased significantly that of the vehicle control. Formation of DNA adducts in the lungs of mice exposed to nanomaterials were also analyzed by stable isotope dilution LC-MS/MS. 8-Oxodeoxyguanosine and other lipid peroxide related adducts were increased by 2- to 5-fold in the nanomaterial-exposed mice. Moreover, multiple (four consecutive doses of 0.2 mg per animal per week) instillations of C60 or kaolin, increased gpt mutant frequencies in the lungs of gpt delta transgenic mice. As the result of mutation spectrum analysis, G:C to C:G transversions were commonly increased in the lungs of mice exposed to both nanomaterials. In addition, G:C to A:T was increased in kaolin-exposed mice. In immunohistochemical analysis, many regions of the lungs that stained positively for nitrotyrosine (NT) were observed in mice exposed to nanomaterials. From these observations, it is suggested that oxidative stress and inflammatory responses are probably involved in the genotoxicity induced by C60 and kaolin.<br>

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