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Investigation of micronized titanium dioxide penetration in human skin xenografts and its effect on cellular functions of human skin-derived cells

Authors

  • Borbála Kiss,

    1. Department of Dermatology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary;
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    • *

      These authors contributed equally to the work.
      This work was carried out in the frame of the ‘NANODERM’ EU Fifth Framework Program Project (‘Quality of skin as a barrier to ultrafine particles’, QLK4-CT-2002-02678).

  • Tamás Bíró,

    1. Department of Physiology, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Debrecen, Hungary;
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    • *

      These authors contributed equally to the work.
      This work was carried out in the frame of the ‘NANODERM’ EU Fifth Framework Program Project (‘Quality of skin as a barrier to ultrafine particles’, QLK4-CT-2002-02678).

  • Gabriella Czifra,

    1. Department of Physiology, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Debrecen, Hungary;
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  • Balázs I. Tóth,

    1. Department of Physiology, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Debrecen, Hungary;
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  • Zsófia Kertész,

    1. Institute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen, Hungary;
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  • Zita Szikszai,

    1. Institute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen, Hungary;
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  • Árpád Zoltán Kiss,

    1. Institute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen, Hungary;
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  • István Juhász,

    1. Department of Dermatology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary;
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  • Christos C. Zouboulis,

    1. Departments of Dermatology and Immunology, Dessau Medical Center, Dessau, Germany
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  • János Hunyadi

    1. Department of Dermatology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary;
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Borbála Kiss, MD, Nagyerdei krt 98, H-4012, Debrecen, Hungary, Tel.: +36 52 442 204, Fax : +36 52 414 632, e-mail: bkiss@med.unideb.hu

Abstract

Abstract:  Titanium dioxide (TiO2) nanoparticles are ubiquitously used materials in everyday life (e.g. paints, household products and plastic goods). However, despite the wide array of common applications, their pathogenetic role was also suggested under certain conditions (e.g. pulmonary neoplasias and lung fibrosis). From a dermatological point of view, it is also of great importance that TiO2 also serves as a physical photoprotective agent in sunscreens and is widely used in various cosmetic products. However, the effect of TiO2 on human cutaneous functions is still unknown. Therefore, in the current study, we investigated the in vivo penetration of TiO2 via human skin transplanted to immunodeficient mice and, furthermore, we measured the in vitro effects of nanoparticles on various functional properties of numerous epidermal and dermal cells in culture. Hereby, using various nuclear microscopy methods, we provide the first evidence that TiO2 nanoparticles in vivo do not penetrate through the intact epidermal barrier. However, we also report that TiO2, when exposed directly to cell cultures in vitro, exerts significant and cell-type dependent effects on such cellular functions as viability, proliferation, apoptosis and differentiation. Therefore, our novel findings will hopefully inspire one to systemically explore in future, clinically oriented trials whether there is indeed a risk from micronized TiO2-containing products on skin with an impaired stratum corneum barrier function.

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