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A Gene Expression Profiling Approach to Study the Influence of Ultrafine Particles on Rat Lungs

  • Katsuhide Fujita
  • Yasuo Morimoto
  • Akira Ogami
  • Isamu Tanaka
  • Shigehisa Endoh
  • Kunio Uchida
  • Hiroaki Tao
  • Mikio Akasaka
  • Masaharu Inada
  • Kazuhiro Yamamoto
  • Hiroko Fukui
  • Mieko Hayakawa
  • Masanori Horie
  • Yoshiro Saito
  • Yasukazu Yoshida
  • Hitoshi Iwahashi
  • Etsuo Niki
  • Junko Nakanishi

Abstract

In recent years, industrial or commercial products incorporating nanomaterials have triggered concerns for human health. Manufactured nanomaterials are unstable and tend to form secondary particles by agglomeration. Little is known about the cytotoxicity induced by nano-sized secondary particles dispersed in aqueous solution. In the present study, we have attempted to disperse ultrafine nickel oxide particles in water (Uf-NiO), characterize the physicochemical properties, and instill into the trachea of rat lungs. Analysis by inductively couple plasma mass spectrometry (ICP-MS) and transmission electron microscope (TEM) revealed that the Uf-NiO particles began to be cleared from the lungs immediately after treatment, and that low levels of the particles were present at 6 months post-instillation. Genome-wide expression analysis using DNA microarray revealed that intratracheal instillation of Uf-NiO particles led to a rapid increase in the expression of chemokines and genes involved in inflammation. These changes were most pronounced at 1 week post-instillation with Uf-NiO. The expression of Mmp12 mRNA, encoding macrophage metalloelastase 12, was strongly induced immediately following intratracheal instillation. However, expression returned to control levels by 6 months post-instillation expression of various other genes categorized into the detection of chemical stimulus were increased at this time point, at which time the inflammatory response had diminished. These results suggest that residual Uf-NiO in the lungs subacutely initiated distinct cellular events through signal transduction after resolution of the inflammatory response. We conclude that gene expression analysis using DNA microarrays can be extremely useful in assessing the influence of utrafine particles on biological systems.

Keywords

Keywords DNA microarray Nano Ultrafine nickel oxide Intratracheal instillation Lung Rat 

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Katsuhide Fujita
    • 1
  • Yasuo Morimoto
    • 2
  • Akira Ogami
    • 3
  • Isamu Tanaka
    • 4
  • Shigehisa Endoh
    • 5
  • Kunio Uchida
    • 6
  • Hiroaki Tao
    • 7
  • Mikio Akasaka
    • 8
  • Masaharu Inada
    • 9
  • Kazuhiro Yamamoto
    • 10
  • Hiroko Fukui
    • 11
  • Mieko Hayakawa
    • 12
  • Masanori Horie
    • 13
  • Yoshiro Saito
    • 14
  • Yasukazu Yoshida
    • 15
  • Hitoshi Iwahashi
    • 16
  • Etsuo Niki
    • 17
  • Junko Nakanishi
    • 18
  1. 1.Health Technology Research Center (HTRC)National Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan
  2. 2.Institute of Industrial Ecological SciencesUniversity of Occupational and Environmental HealthKitakyushuJapan
  3. 3.Institute of Industrial Ecological SciencesUniversity of Occupational and Environmental HealthKitakyushuJapan
  4. 4.Institute of Industrial Ecological SciencesUniversity of Occupational and Environmental HealthKitakyushuJapan
  5. 5.Research Institute for Environmental Management Technology (EMTECH), National Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan
  6. 6.Research Institute for Environmental Management Technology (EMTECH), National Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan
  7. 7.Research Institute for Environmental Management Technology (EMTECH), National Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan
  8. 8.Research Institute for Environmental Management Technology (EMTECH), National Institute of Advanced Industrial Science and Technology (AIST), Industrial Technology Association (JITA)TsukubaJapan
  9. 9.Research Institute for Environmental Management Technology (EMTECH), National Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan
  10. 10.Research Institute of Instrumentation Frontier (RIIF), National Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan
  11. 11.National Institute of Advanced Industrial Science and Technology (AIST)Health Technology Research Center (HTRC)Osaka, 563-8577Japan
  12. 12.National Institute of Advanced Industrial Science and Technology (AIST)Health Technology Research Center (HTRC)Osaka, 563-8577Japan
  13. 13.National Institute of Advanced Industrial Science and Technology (AIST)Health Technology Research Center (HTRC)Osaka, 563-8577Japan
  14. 14.National Institute of Advanced Industrial Science and Technology (AIST)Health Technology Research Center (HTRC)Osaka, 563-8577Japan
  15. 15.National Institute of Advanced Industrial Science and Technology (AIST)Health Technology Research Center (HTRC)Osaka, 563-8577Japan
  16. 16.National Institute of Advanced Industrial Science and TechnologyHealth Technology Research CenterOsaka, 563-8577Japan
  17. 17.National Institute of Advanced Industrial Science and Technology (AIST)Health Technology Research Center (HTRC)Osaka, 563-8577Japan
  18. 18.Nakanishi, Research Institute of Science for Safety and Sustainability (RISS), National Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan

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