A comprehensive study of the harmful effects of ZnO nanoparticles using Drosophila melanogaster as an in vivo model.

This study planned to determine the range of biological effects associated with ZnO-NP exposure using Drosophila melanogaster as an in vivo model. In addition, ZnCl2 was used to determine the potential role of Zn ions alone. Toxicity, internalization through the intestinal barrier, gene expression changes, ROS production, and genotoxicity were the end-points evaluated. No toxicity or oxidative stress induction was observed in D. melanogaster larvae, whether using ZnO-NPs or ZnCl2. Internalization of ZnO-NPs through the intestinal barrier was observed. No significant changes in the frequency of mutant clones (wing-spot test) or percentage of DNA in tail (comet assay) were observed although significant changes in Hsp70 and p53 gene expression were detected. Our study shows that ZnO-NPs do not induce toxicity or genotoxicity in D. melanogaster, although uptake occurs and altered gene expression is observed.

[1]  R. Marcos,et al.  Antioxidant and antigenotoxic properties of CeO2 NPs and cerium sulphate: Studies with Drosophila melanogaster as a promising in vivo model , 2015, Nanotoxicology.

[2]  Cayetano Gonzalez,et al.  Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics , 2013, Nature Reviews Cancer.

[3]  M Gribskov,et al.  A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. , 2001, Genome research.

[4]  David Kirkland,et al.  Clastogenicity, photo-clastogenicity or pseudo-photo-clastogenicity: Genotoxic effects of zinc oxide in the dark, in pre-irradiated or simultaneously irradiated Chinese hamster ovary cells. , 2006, Mutation research.

[5]  S. Hussain,et al.  Silver nanoparticles induced heat shock protein 70, oxidative stress and apoptosis in Drosophila melanogaster. , 2010, Toxicology and applied pharmacology.

[6]  M. Camatini,et al.  Evidence and uptake routes for Zinc oxide nanoparticles through the gastrointestinal barrier in Xenopus laevis , 2013, Nanotoxicology.

[7]  Sanjay Mathur,et al.  In vitro mechanistic study towards a better understanding of ZnO nanoparticle toxicity , 2013, Nanotoxicology.

[8]  G. Vecchio A fruit fly in the nanoworld: once again Drosophila contributes to environment and human health , 2015, Nanotoxicology.

[9]  X. Sima,et al.  Effects of nano-scale TiO2, ZnO and their bulk counterparts on zebrafish: acute toxicity, oxidative stress and oxidative damage. , 2011, The Science of the total environment.

[10]  K. Kasemets,et al.  Toxicity of nanoparticles of CuO, ZnO and TiO2 to microalgae Pseudokirchneriella subcapitata. , 2009, The Science of the total environment.

[11]  Han-Woong Lee,et al.  Essential role of p53 in TPEN‐induced neuronal apoptosis , 2009, FEBS letters.

[12]  João Paulo Teixeira,et al.  Neuronal cytotoxicity and genotoxicity induced by zinc oxide nanoparticles. , 2013, Environment international.

[13]  Nick Serpone,et al.  Inorganic and organic UV filters: Their role and efficacy in sunscreens and suncare products , 2007 .

[14]  D. K. Chowdhuri,et al.  Cellular internalization and stress response of ingested amorphous silica nanoparticles in the midgut of Drosophila melanogaster. , 2013, Biochimica et biophysica acta.

[15]  Peng Wang,et al.  Toxicity of zinc oxide nanoparticles in the earthworm, Eisenia fetida and subcellular fractionation of Zn. , 2011, Environment international.

[16]  R. Marcos,et al.  Genotoxicity of cobalt nanoparticles and ions in Drosophila , 2013, Nanotoxicology.

[17]  Dennis Wilson,et al.  Uptake and inflammatory effects of nanoparticles in a human vascular endothelial cell line. , 2009, Research report.

[18]  R. Schiestl,et al.  Role of homologous recombination in carcinogenesis. , 2003, Experimental and molecular pathology.

[19]  S. Tubek,et al.  Role of Zinc in Hemostasis: A Review , 2007, Biological Trace Element Research.

[20]  R. Marcos,et al.  Genotoxicity and DNA Repair Processes of Zinc Oxide Nanoparticles , 2014, Journal of toxicology and environmental health. Part A.

[21]  M. Çulha,et al.  Influence of surface properties of zinc oxide nanoparticles on their cytotoxicity. , 2014, Colloids and surfaces. B, Biointerfaces.

[22]  I. Hsiao,et al.  Effects of serum on cytotoxicity of nano- and micro-sized ZnO particles , 2013, Journal of Nanoparticle Research.

[23]  Diana Anderson,et al.  Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2) , 2012, Apoptosis.

[24]  D. K. Saxena,et al.  Hazardous effects of effluent from the chrome plating industry: 70 kDa heat shock protein expression as a marker of cellular damage in transgenic Drosophila melanogaster (hsp70-lacZ). , 2003, Environmental health perspectives.

[25]  Rahul,et al.  Toxic Potential of Synthesized Graphene Zinc Oxide Nanocomposite in the Third Instar Larvae of Transgenic Drosophila melanogaster (hsp70-lacZ)Bg 9 , 2014, BioMed research international.

[26]  Timothy F Hoban,et al.  Sleep disorders in children , 2010, Annals of the New York Academy of Sciences.

[27]  Purusottam Mohapatra,et al.  Silver-based nanoparticles induce apoptosis in human colon cancer cells mediated through p53. , 2013, Nanomedicine.

[28]  S. Hackenberg,et al.  Cytotoxic, genotoxic and pro-inflammatory effects of zinc oxide nanoparticles in human nasal mucosa cells in vitro. , 2011, Toxicology in vitro : an international journal published in association with BIBRA.

[29]  R. Marcos,et al.  Proposal of an in vivo comet assay using haemocytes of Drosophila melanogaster , 2011, Environmental and molecular mutagenesis.

[30]  Pei-Shan Liu,et al.  Zinc oxide nanoparticles interfere with zinc ion homeostasis to cause cytotoxicity. , 2012, Toxicological sciences : an official journal of the Society of Toxicology.

[31]  O. Kovalchuk,et al.  Does bacterial infection cause genome instability and cancer in the host cell? , 2014, Mutation research.

[32]  Ruchi Roy,et al.  Mechanism of uptake of ZnO nanoparticles and inflammatory responses in macrophages require PI3K mediated MAPKs signaling. , 2014, Toxicology in vitro : an international journal published in association with BIBRA.

[33]  Anne Kahru,et al.  Toxicity of nanosized and bulk ZnO, CuO and TiO2 to bacteria Vibrio fischeri and crustaceans Daphnia magna and Thamnocephalus platyurus. , 2008, Chemosphere.

[34]  Steffen Loft,et al.  Oxidatively damaged DNA in animals exposed to particles , 2013, Critical reviews in toxicology.

[35]  M A Kastenbaum,et al.  Tables for determining the statistical significance of mutation frequencies. , 1970, Mutation research.

[36]  T. Scarabelli,et al.  Metallic nanoparticles and their medicinal potential. Part II: aluminosilicates, nanobiomagnets, quantum dots and cochleates. , 2013, Therapeutic delivery.

[37]  M. Ahamed,et al.  ZnO nanorod-induced apoptosis in human alveolar adenocarcinoma cells via p53, survivin and bax/bcl-2 pathways: role of oxidative stress. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[38]  J. Taylor,et al.  Flightless flies: Drosophila models of neuromuscular disease , 2010, Annals of the New York Academy of Sciences.

[39]  J. Schulz,et al.  Drosophila melanogaster as a model organism for Alzheimer’s disease , 2013, Molecular Neurodegeneration.

[40]  C. Nichols,et al.  Human Disease Models in Drosophila melanogaster and the Role of the Fly in Therapeutic Drug Discovery , 2011, Pharmacological Reviews.

[41]  B. Bay,et al.  Drosophila melanogaster as a model organism to study nanotoxicity , 2015, Nanotoxicology.

[42]  R. Handy,et al.  C60 exposure induced tissue damage and gene expression alterations in the earthworm Lumbricus rubellus , 2013, Nanotoxicology.

[43]  J. Kwon,et al.  Lack of genotoxic potential of ZnO nanoparticles in in vitro and in vivo tests. , 2014, Mutation research. Genetic toxicology and environmental mutagenesis.

[44]  G. Nohynek,et al.  Nano-sized cosmetic formulations or solid nanoparticles in sunscreens: A risk to human health? , 2012, Archives of Toxicology.

[45]  M. Valko,et al.  Advances in metal-induced oxidative stress and human disease. , 2011, Toxicology.

[46]  S. Ryter,et al.  Mechanisms of cell death in oxidative stress. , 2007, Antioxidants & redox signaling.

[47]  Rongfa Guan,et al.  Cytotoxicity, oxidative stress, and genotoxicity in human hepatocyte and embryonic kidney cells exposed to ZnO nanoparticles , 2012, Nanoscale Research Letters.

[48]  Chung‐Che Wu,et al.  Organ biodistribution, clearance, and genotoxicity of orally administered zinc oxide nanoparticles in mice , 2012, Nanotoxicology.