Genotoxicity analysis of rutile titanium dioxide nanoparticles in mice after 28 days of repeated oral administration

Abstract

Titanium dioxide (TiO2) or titania has demonstrated excellent potential for commercial use in various arenas, such as in the paint, in pharmaceuticals and food industry. However information on the genotoxic potential of rutile form of TiO2-NP after repeated (28 days) low dose oral exposure in major organs of the reticuloendothelial system (liver, spleen, bone marrow, lymph nodes) is not known. In this study Swiss albino male mice were gavaged TiO2-NP at sub-acute concentration (0.2, 0.4 and 0.8 mg/kg body weight) over a period of 28 days. Results revealed that TiO2-NP administered was of rutile form with mean average size of 25 nm by transmission electron microscopy. The values of PDI and Zeta potential from DLS of TiO2-NP in suspension specified that the nanomaterial was stable without much agglomeration. Chromosomal aberration assay showed that TiO2-NP was genotoxic and cytotoxic. DNA damage evaluation by comet assay confirmed that long term exposure to TiO2-NP at low concentrations can induce genotoxicity systemically in organs, such as liver, spleen, and thymus cells. Structural chromosomal aberration test from bone marrow cells revealed the clastogenicity of TiO2-NP at sub chronic low concentrations. Further in vivo studies are needed to elucidate the underlying mechanisms at the molecular level.

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Acknowledgements

J. Manivannan would like to acknowledge the University Grants Commission for financial assistance in the form of Research Fellowship under the Basic Scientific Research scheme (Sanction No. F.5- 21/2007dt 12.03.2014). For instrumentation facilities the authors would like to acknowledge UGC-Center for Research in Nano Science, University of Calcutta.

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Correspondence to Anita Mukherjee.

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Manivannan, J., Banerjee, R. & Mukherjee, A. Genotoxicity analysis of rutile titanium dioxide nanoparticles in mice after 28 days of repeated oral administration. Nucleus 63, 17–24 (2020). https://doi.org/10.1007/s13237-019-00277-0

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Keywords

  • Clastogenicity
  • Comet assay
  • DNA damage
  • Genotoxicity
  • Rutile titania
  • Swiss albino mice