Genotoxicity of nano-silica in mammalian cell lines

  • Han-Saem Choi
  • Youn-Jung Kim
  • Mee Song
  • Mi-Kyung Song
  • Jae-Chun Ryu
Research Article


Nanomaterials are defined by the U.S. National Nanotechnology Initiative as materials that have at least one dimension in the 1- to 100-nm range. Due to their unique physical and chemical characteristics, nanotechnology has become one of the leading technologies over the past 10 years. This study represents data on genotoxic effects of nanoparticles and their application for assessing human health risks. Silica (SiO2) is a multi-functional ceramic material that is being used in various industries to improve surfaces and mechanical properties of diverse materials, such as paints and coatings, plastics, synthetic rubber, adhesives, sealants, or insulation materials. However, recent studies have shown that nano-sized silica (nano-silica) (10 nm in diameter) can generate adverse effects, like liver injury and inflammation. The cytotoxicity and genotoxicity of nano-silica were investigated using the dye exclusion assay, comet assay, and mouse lymphoma thymidine kinase (tk +/−) mouse lymphoma assay (MLA). IC20 of nano-silica in L5178Y cells was determined to be of 2,441.41 μg/mL and 2,363.28 μg/mL without and with S-9, respectively. Also IC20 of nano-silica in BEAS-2B cells was determined to be of 2,324.23 μg/mL and 537.11 μg/mL without and with S-9, respectively. In the comet assay, treating L5178Y cells and BEAS-2B cells with nanosilica treatment induced approximately 2-fold increases in tail moment (P<0.05) without and with S-9. Also, the mutant frequencies in the nano-silica treated L5178Y cells were not significantly increased compared to the solvent controls. The results of this study indicate that nano-silica can cause primary DNA damage and cytotoxicity but not mutagenicity in cultured mammalian cells.


Nanoparticle Nano-silica Comet assay Mouse lymphoma assay (MLA) Cytotoxicity Genotoxicity 


  1. 1.
    Dey, S. et al. Interactions between SIRT1 and AP-1 reveal a mechanistic insight into the growth promoting properties of alumina (Al2O3) nanoparticles in mouse skin epithelial cells. Carcinogenesis. 29, 1920–1929 (2008).PubMedCrossRefGoogle Scholar
  2. 2.
    Balasubramanyam, A. et al. In vivo genotoxicity assessment of aluminium oxide nanomaterials in rat peripheral blood cells using the comet assay and micronucleus test. Mutagenesis. 24, 245–251 (2009).PubMedCrossRefGoogle Scholar
  3. 3.
    Colvin, V. L. The potential environmental impact of engineered nanomaterials. Nat. Biotechnol. 21, 1166–1170 (2003).PubMedCrossRefGoogle Scholar
  4. 4.
    Oberdörster, G., Oberdörster, E. & Oberdörster, J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 113, 823–839 (2005).PubMedCrossRefGoogle Scholar
  5. 5.
    Aillon, K. L. et al. Effects of nanomaterial physicochemical properties on in vivo toxicity. Adv. Drug. Deliv. Rev. 61, 457–466 (2009).PubMedCrossRefGoogle Scholar
  6. 6.
    Hirsch, L. R. et al. Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proc. Natl. Acad. Sci. 100, 13549–13554 (2003).PubMedCrossRefGoogle Scholar
  7. 7.
    Moghimi, S. M., Hunter, A. C. & Murray, J. C. Nanomedicine: current status and future prospects. FASEB J. 19, 311–330 (2005).PubMedCrossRefGoogle Scholar
  8. 8.
    Ravi Kumar, M. N. V. et al. Cationic silica nanoparticles as gene carriers: synthesis, characterization and transfection efficiency in vitro and in vivo. J. Nanosci. Nanotechnol. 4, 876–881 (2004).PubMedCrossRefGoogle Scholar
  9. 9.
    Slowing, I. I. et al. Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv. Drug. Deliv. Rev. 60, 1278–1288 (2008).PubMedCrossRefGoogle Scholar
  10. 10.
    Vijayanathan, V., Thomas, T. & Thomas, T. J. DNA nanoparticles and development of DNA delivery vehicles for gene therapy. Biochemistry 41, 14085–14094 (2002).PubMedCrossRefGoogle Scholar
  11. 11.
    Eom, H. J. & Choi, J. Oxidative stress of silica nanoparticles in human bronchial epithelial cell, Beas-2B. Toxicol. In Vitro 23, 1326–1332 (2009).PubMedCrossRefGoogle Scholar
  12. 12.
    Ye, Y. et al. Nano-SiO2 induces apoptosis via activation of p53 and Bax mediated by oxidative stress in human hepatic cell line. Toxicol. In Vitro 24, 751–758 (2010).PubMedCrossRefGoogle Scholar
  13. 13.
    Warheit, D. B. et al. Pulmonary bioassay studies with nanoscale and fine-quartz particles in rats: toxicity is not dependent upon particle size but on surface characteristics. Toxicol. Sci. 95, 270–280 (2007).PubMedCrossRefGoogle Scholar
  14. 14.
    Chen, Y., Chen, J., Dong, J. & Jin, Y. Comparing study of the effect of nanosized silicon dioxide and microsized silicon dioxide on fibrogenesis in rats. Toxicol. Ind. Health 20, 21–27 (2004).PubMedCrossRefGoogle Scholar
  15. 15.
    Chen, M. & von Mikecz, A. Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Exp. Cell Res. 305, 51–62 (2005).PubMedCrossRefGoogle Scholar
  16. 16.
    Xue, Z. G. et al. Biotoxicology and biodynamics of silica nanoparticle. J. Cent. South Univ. 31, 6–8 (2006).Google Scholar
  17. 17.
    Singh, N. P., McCoy, M. T., Tice, R. R. & Schneider, E. L. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp. Cell. Res. 175, 184–191 (1988).PubMedCrossRefGoogle Scholar
  18. 18.
    Tice, R. R. et al. The single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ. Mol. Mutagen 35, 206–221 (2000).PubMedCrossRefGoogle Scholar
  19. 19.
    Anderson, D. & Plewa, M. J. The international comet assay workshop. Mutagenesis 13, 67–73 (1998).PubMedCrossRefGoogle Scholar
  20. 20.
    Fairbairn, D. W., Walburger, D. K., Fairbairn, J. J. & O’Neill, K. L. Key morphologic changes and DNA strand breaks in human lymphoid cells: discriminating apoptosis from necrosis. Scanning 18, 407–416 (1996).PubMedCrossRefGoogle Scholar
  21. 21.
    Speit, G. & Hartmann, A. The comet assay (single-cell gel test). A sensitive genotoxicity test for the detection of DNA damage and repair. Methods. Mol. Biol. 113, 203–212 (1999).PubMedGoogle Scholar
  22. 22.
    Lockman, P. R. et al. In vivo and in vitro assessment of baseline bloodbrain barrier parameters in the presence of novel nanoparticles. Pharm. Res. 20, 705–713 (2003).PubMedCrossRefGoogle Scholar
  23. 23.
    Braydich-Stolle, L., Hussain, S., Schlager, J. J. & Hofmann, M. C. In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. Toxicol. Sci. 88, 412–419 (2005).PubMedCrossRefGoogle Scholar
  24. 24.
    Yang, L. & Watts, D. J. Particle surface characteristics may play an important role in phytotoxicity of alumina nanoparticles. Toxicol. Lett. 158, 122–132 (2005).PubMedCrossRefGoogle Scholar
  25. 25.
    Akhtar, M. J. et al. Nanotoxicity of pure silica mediated through oxidant generation rather than glutathione depletion in human lung epithelial cells. Toxicology 276, 95–102 (2010).PubMedCrossRefGoogle Scholar
  26. 26.
    Merchant, R. K., Peterson, M. W. & Hunninghake, G. W. Silica directly increases permeability of alveolar epithelial cells. J. Appl. Physiol. 68, 1354–1359 (1990).PubMedCrossRefGoogle Scholar
  27. 27.
    Chen, J. et al. Silica increases cytosolic free calcium ion concentration of alveolar macrophages in vitro. Toxicol. Appl. Pharmacol. 111, 211–220 (1991).PubMedCrossRefGoogle Scholar
  28. 28.
    Gerloff, K. et al. Cytotoxicity and oxidative DNA damage by nanoparticles in human intestinal Caco-2 cells. Nanotoxicology 3, 355–364. (2009).CrossRefGoogle Scholar
  29. 29.
    Gonzalez, L. et al. Exploring the aneugenic and clastogenic potential in the nanosize range: A549 human lung carcinoma cells and amorphous monodisperse silica nanoparticles as models. Nanotoxicology 4, 382–395 (2010).PubMedCrossRefGoogle Scholar
  30. 30.
    Ames, B. N., Durston, W. E., Yamasaki, E. & Lee, F. D. Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc. Natl. Acad. Sci. USA 70, 2281–2285 (1973).PubMedCrossRefGoogle Scholar
  31. 31.
    Clements, J. In vitro Toxicity Testing Protocols Vol. 43 (eds O’Hare, S. & Atterwill, C. K.) 277–286 (Humana Press Inc. Totowa, NJ, 1990).Google Scholar
  32. 32.
    Robinson, W. D. et al. in Statistical Evaluation of Mutagenicity Test Data (eds Kirkland, D. J.) 102–140 (Cambridge University Press. Cambridge, UK, 1990).Google Scholar

Copyright information

© Korean Society of Environmental Risk Assessment and Health Science and Springer 2011

Authors and Affiliations

  • Han-Saem Choi
    • 1
  • Youn-Jung Kim
    • 2
  • Mee Song
    • 1
  • Mi-Kyung Song
    • 1
  • Jae-Chun Ryu
    • 1
  1. 1.Cellular and Molecular Toxicology LaboratoryKorea Institute of Science & TechnologyCheongryang, SeoulKorea
  2. 2.Department of Applied ChemistryKyung Hee UniversityYonginKorea

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