Journal of Hazardous Materials 264 (2014) 420–429 Contents lists available at ScienceDirect Journal of Hazardous Materials jou rn al hom epage: www.elsevier.com/locate/jhazmat Zinc oxide nanoparticles: Genotoxicity, interactions with UV-light and cell-transforming potential Es ¸ ref Demir a , Hakan Akc ¸ a b , Bülent Kaya a , Durmus ¸ Burgucu c , Onur Tokgün b , Fatma Turna a , Sezgin Aksakal a , Gerard Vales d , Amadeu Creus d,e , Ricard Marcos d,e,∗ a Akdeniz University, Faculty of Sciences, Department of Biology, 07058 Antalya, Turkey b Medical Biology Department, School of Medicine, Pamukkale University, Kinikli, Denizli, Turkey c Akdeniz University, Faculty of Medicine, Department of Physiology, 07058 Antalya, Turkey d Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Campus de Bellaterra, 08193 Cerdanyola del Vallès, Spain e CIBER Epidemiología y Salud Pública, ISCIII, Spain h i g h l i g h t s • Genotoxicity of ZnO NPs has been shown in mammalian cells. • ZnO NPs has been able to induce cell transformation. • An antagonist interaction between ZnO NPs and UVB-light has been demonstrated. • Genotoxic/carcinogenic effects differ between ZnO NPs and the ionic forms. a r t i c l e i n f o Article history: Received 23 May 2013 Received in revised form 12 November 2013 Accepted 14 November 2013 Available online 25 November 2013 Keywords: ZnO nanoparticles Comet assay Micronucleus assay Soft-agar assay Genotoxicity UV-light interaction a b s t r a c t The in vitro genotoxic and the soft agar anchorage independent cell transformation ability of zinc oxide nanoparticles (NPs) and its bulky forms have been evaluated in human embryonic kidney (HEK293) and in mouse embryonic fibroblast (NIH/3T3) cells, either alone or in combination with UVB-light. The comet assay, with and without the use of FPG and Endo III enzymes, the micronucleus assay and the soft-agar colony assay were used. For the comet assay a statistically significant induction of DNA damage, with and without the enzymes, were observed up of 100 g/mL. ZnO NPs were able to increase significantly the frequency of micronuclei, and similar results were observed in the cell transformation assay where such NPs were able to induce cell-anchorage independent growth. These effects were observed at doses up 100 g/mL. Although UVB-light was able to induce genotoxic damage and cell-anchorage growth, a significant antagonist interaction effect was observed in combination with ZnO NPs. These in vitro results, obtained with the selected cell lines, contribute to increase our genotoxicity database on the ZnO NPs effects as well as to open the discussion about their risk in photo-protection sun screens. © 2013 Elsevier B.V. All rights reserved. 1. Introduction The industrial applications of nanotechnology are rapidly increasing due to the new and interesting physicochemical prop- erties of the produced nanomaterials. The wide expansion of this market implies the growing presence of such materials in our surrounding environment. Thus, although human exposure to ∗ Corresponding author at: Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Campus de Bellaterra, 08193 Cerdanyola del Vallès, Spain. Tel.: +34 935812052; fax: +34 935812387. E-mail address: ricard.marcos@uab.es (R. Marcos). nanoparticles (NPs) is certainly occurring at present, a very dra- matic increase is expected in the near future [1]. Nanomaterials are defined by their small size, with at least one dimension less than 100 nm, and their novel physicochemical properties. Among nanomaterials, different metal nanoparticles are among the most used. The high biological reactivity of nanomet- als, in comparison with their corresponding bulk materials, may suggest an increased toxicity, including the genetic material as a target. For these reasons, nanotoxicology and nanogenotoxi- cology are extending as novel fields, looking for the potential risk of nanomaterials as well as for their possible mechanisms of action [2–6]. Among nanomaterials, zinc oxide nanoparticles (ZnO NPs) are widely used in industrial products including cosmetics, sunscreens, 0304-3894/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jhazmat.2013.11.043