title: Investigation of micronized titanium dioxide penetration in human skin xenografts and its effect on cellular functions of human skin-derived cells.
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 TiO2nanoparticles 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.
authors.affiliation: Department of Dermatology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary. bkiss@med.unideb.hu
authors.forename: Borbála
authors.initials: B
authors.lastname: Kiss
authors.forename: Tamás
authors.initials: T
authors.lastname: Bíró
authors.forename: Gabriella
authors.initials: G
authors.lastname: Czifra
authors.forename: Balázs I
authors.initials: BI
authors.lastname: Tóth
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Kertész
authors.forename: Zita
authors.initials: Z
authors.lastname: Szikszai
authors.forename: Arpád Zoltán
authors.initials: AZ
authors.lastname: Kiss
authors.forename: István
authors.initials: I
authors.lastname: Juhász
authors.forename: Christos C
authors.initials: CC
authors.lastname: Zouboulis
authors.forename: János
authors.initials: J
authors.lastname: Hunyadi
mesh_terms: D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D016513:Mice, SCID; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016038:Skin Transplantation; D013473:Sunscreening Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D014025:Titanium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000633:toxicity; D014183:Transplantation, Heterologous
chemical_list: D013473:Sunscreening Agents; C009495:titanium dioxide; D014025:Titanium