Skip to main content

Advertisement

Log in

Microscopy-based high-throughput assays enable multi-parametric analysis to assess adverse effects of nanomaterials in various cell lines

  • Nanotoxicology
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

A Data Descriptor to this article was published on 02 May 2019

Abstract

Manufactured nanomaterials (MNMs) selected from a library of over 120 different MNMs with varied compositions, sizes, and surface coatings were tested by four different laboratories for toxicity by high-throughput/-content (HT/C) techniques. The selected particles comprise 14 MNMs composed of CeO2, Ag, TiO2, ZnO and SiO2 with different coatings and surface characteristics at varying concentrations. The MNMs were tested in different mammalian cell lines at concentrations between 0.5 and 250 µg/mL to link physical–chemical properties to multiple adverse effects. The cell lines are derived from relevant organs such as liver, lung, colon and the immune system. Endpoints such as viable cell count, cell membrane permeability, apoptotic cell death, mitochondrial membrane potential, lysosomal acidification and steatosis have been studied. Soluble MNMs, Ag and ZnO, were toxic in all cell types. TiO2 and SiO2 MNMs also triggered toxicity in some, but not all, cell types and the cell type-specific effects were influenced by the specific coating and surface modification. CeO2 MNMs were nearly ineffective in our test systems. Differentiated liver cells appear to be most sensitive to MNMs, Whereas most of the investigated MNMs showed no acute toxicity, it became clear that some show adverse effects dependent on the assay and cell line. Hence, it is advised that future nanosafety studies utilise a multi-parametric approach such as HT/C screening to avoid missing signs of toxicity. Furthermore, some of the cell type-specific effects should be followed up in more detail and might also provide an incentive to address potential adverse effects in vivo in the relevant organ.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Al-Rawi M, Diabaté S, Weiss C (2011) Uptake and intracellular localization of submicron and nano-sized SiO(2) particles in HeLa cells. Arch Toxicol 85:813–826

    Article  CAS  PubMed  Google Scholar 

  • Anguissola S, Garry D, Salvati A, O’Brien PJ, Dawson KA (2014) High content analysis provides mechanistic insights on the pathways of toxicity induced by amine-modified polystyrene nanoparticles. PLoS One 9:e108025

    Article  PubMed  PubMed Central  Google Scholar 

  • Armand L, Tarantini A, Beal D, Biola-Clier M, Bobyk L, Sorieul S, Pernet-Gallay K, Marie-Desvergne C, Lynch I, Herlin-Boime N, Carriere M (2016) Long-term exposure of A549 cells to titanium dioxide nanoparticles induces DNA damage and sensitizes cells towards genotoxic agents. Nanotoxicology 10:913–923

    Article  CAS  PubMed  Google Scholar 

  • Cerec V, Glaise D, Garnier D, Morosan S, Turlin B, Drenou B, Gripon P, Kremsdorf D, Guguen-Guillouzo C, Corlu A (2007) Transdifferentiation of hepatocyte-like cells from the human hepatoma HepaRG cell line through bipotent progenitor. Hepatology 45:957–967

    Article  CAS  PubMed  Google Scholar 

  • Cho WS, Duffin R, Howie SE, Scotton CJ, Wallace WA, MacNee W, Bradley M, Megson IL, Donaldson K (2011) Progressive severe lung injury by zinc oxide nanoparticles; the role of Zn2+ dissolution inside lysosomes. Part Fibre Toxicol 8:27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Vandebriel RJ, Jong WH (2012) A review of mammalian toxicity of ZnO nanoparticles. Nanotechnol Sci Appl 5:61–71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Delaval M, Wohlleben W, Landsiedel R, Baeza-Squiban A, Boland S (2017) Assessment of the oxidative potential of nanoparticles by the cytochrome c assay: assay improvement and development of a high-throughput method to predict the toxicity of nanoparticles. Arch Toxicol 91:163–177

    Article  CAS  PubMed  Google Scholar 

  • DeLoid G, Cohen JM, Darrah T, Derk R, Rojanasakul L, Pyrgiotakis G, Wohlleben W, Demokritou P (2014) Estimating the effective density of engineered nanomaterials for in vitro dosimetry. Nat Commun 5:3514

    Article  PubMed  Google Scholar 

  • DeLoid GM, Cohen JM, Pyrgiotakis G, Pirela SV, Pal A, Liu J, Srebric J, Demokritou P (2015) Advanced computational modeling for in vitro nanomaterial dosimetry. Part Fibre Toxicol 12:32

    Article  PubMed  PubMed Central  Google Scholar 

  • DeLoid GM, Cohen JM, Pyrgiotakis G, Demokritou P (2017) Preparation, characterization, and in vitro dosimetry of dispersed, engineered nanomaterials. Nat Protoc 12:355–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deschamps E, Weidler PG, Friedrich F, Weiss C, Diabaté S (2014) Characterization of indoor dust from Brazil and evaluation of the cytotoxicity in A549 lung cells. Environ Geochem Health 36:225–233

    Article  CAS  PubMed  Google Scholar 

  • Dilger M, Orasche J, Zimmermann R, Paur HR, Diabaté S, Weiss C (2016) Toxicity of wood smoke particles in human A549 lung epithelial cells: the role of PAHs, soot and zinc. Arch Toxicol 90:3029–3044

    Article  CAS  PubMed  Google Scholar 

  • Donauer J, Schreck I, Liebel U, Weiss C (2012) Role and interaction of p53, BAX and the stress-activated protein kinases p38 and JNK in benzo(a)pyrene-diolepoxide induced apoptosis in human colon carcinoma cells. Arch Toxicol 86:329–337

    Article  CAS  PubMed  Google Scholar 

  • ECHA (2016) Proposal for harmonised classification and labelling. Substance name: Titanium dioxide. European Chemicals Agency. https://echa.europa.eu/documents/10162/594bf0e6-8789-4499-b9ba-59752f4eafab. Accessed 7 Nov 2017

  • Efeyan A, Serrano M (2007) p53: guardian of the genome and policeman of the oncogenes. Cell Cycle 6:1006–1010

    Article  CAS  PubMed  Google Scholar 

  • European commission (2013) Examination and assessment of consequences for industry, consumers, human health and the environment of possible options for changing the REACH requirements for nanomaterials. Final report. http://ec.europa.eu/environment/chemicals/nanotech/pdf/Final_Report.pdf. Joint Research Centre, Institute for Health and Consumer Protection, Reference: IHCP/2011/I/05/27/OC. Accessed 7 Nov 2017

  • Gebel T, Foth H, Damm G, Freyberger A, Kramer PJ, Lilienblum W, Röhl C, Schupp T, Weiss C, Wollin KM, Hengstler JG (2014) Manufactured nanomaterials: categorization and approaches to hazard assessment. Arch Toxicol 88:2191–2211

    Article  CAS  PubMed  Google Scholar 

  • Gerloff K, Landesmann B, Worth A, Munn S, Palosaari T, Whelan M (2017) The adverse outcome pathway appoach in nanotoxicology. Comput Toxicol 1:3–11

    Article  Google Scholar 

  • Godoy P, Hewitt NJ, Albrecht U, Andersen ME, Ansari N, Bhattacharya S, Bode JG, Bolleyn J, Borner C, Bottger J, Braeuning A, Budinsky RA, Burkhardt B, Cameron NR, Camussi G, Cho CS, Choi YJ, Craig RJ, Dahmen U, Damm G, Dirsch O, Donato MT, Dong J, Dooley S, Drasdo D, Eakins R, Ferreira KS, Fonsato V, Fraczek J, Gebhardt R, Gibson A, Glanemann M, Goldring CE, Gomez-Lechon MJ, Groothuis GM, Gustavsson L, Guyot C, Hallifax D, Hammad S, Hayward A, Haussinger D, Hellerbrand C, Hewitt P, Hoehme S, Holzhutter HG, Houston JB, Hrach J, Ito K, Jaeschke H, Keitel V, Kelm JM, Kevin PB, Kordes C, Kullak-Ublick GA, LeCluyse EL, Lu P, Luebke-Wheeler J, Lutz A, Maltman DJ, Matz-Soja M, McMullen P, Merfort I, Messner S, Meyer C, Mwinyi J, Naisbitt DJ, Nussler AK, Olinga P, Pampaloni F, Pi J, Pluta L, Przyborski SA, Ramachandran A, Rogiers V, Rowe C, Schelcher C, Schmich K, Schwarz M, Singh B, Stelzer EH, Stieger B, Stober R, Sugiyama Y, Tetta C, Thasler WE, Vanhaecke T, Vinken M, Weiss TS, Widera A, Woods CG, Xu JJ, Yarborough KM, Hengstler JG (2013) Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Arch Toxicol 87:1315–1530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gordon T, Fine JM (1993) Metal fume fever. Occup Med 8:504–517

    CAS  PubMed  Google Scholar 

  • Hoppstädter J, Seif M, Dembek A, Cavelius C, Huwer H, Kraegeloh A, Kiemer AK (2015) M2 polarization enhances silica nanoparticle uptake by macrophages. Front Pharmacol 6:55

    Article  PubMed  PubMed Central  Google Scholar 

  • Horvat T, Landesmann B, Lostia A, Vinken M, Munn S, Whelan M (2017) Adverse outcome pathway development from protein alkylation to liver fibrosis. Arch Toxicol 91:1523–1543

    Article  CAS  PubMed  Google Scholar 

  • Hussain S, Thomassen LCJ, Ferecatu I, Borot MC, Andreau K, Martens JA, Fleury J, Baeza-Squiban A, Marano F, Boland S (2010) Carbon black and titanium dioxide nanoparticles elicit distinct apoptotic pathways in bronchial epithelial cells. Part Fibre Toxicol 7:10

    Article  PubMed  PubMed Central  Google Scholar 

  • Jensen KA, Kembouche Y, Christiansen E, Jacobsen NR, Wallin H, Guiot C, Spalla O, Witschger O (2011) Final protocol for producing suitable manufactured nanomaterial exposure media—standard operation procedure (SPO) and background documentation. NanoGenoTox report. https://www.anses.fr/en/system/files/nanogenotox_deliverable_5.pdf. Accessed 7 Nov 2017

  • Jensen-Waern M, Melin L, Lindberg R, Johannisson A, Petersson L, Wallgren P (1998) Dietary zinc oxide in weaned pigs—effects on performance, tissue concentrations, morphology, neutrophil functions and faecal microflora. Res Vet Sci 64:225–231

    Article  CAS  PubMed  Google Scholar 

  • Johnston HJ, Hutchison GR, Christensen FM, Peters S, Hankin S, Stone V (2009) Identification of the mechanisms that drive the toxicity of TiO(2)particulates: the contribution of physicochemical characteristics. Part Fibre Toxicol 6:33

    Article  PubMed  PubMed Central  Google Scholar 

  • Johnston HJ, Hutchison G, Christensen FM, Peters S, Hankin S, Stone V (2010) A review of the in vivo and in vitro toxicity of silver and gold particulates: particle attributes and biological mechanisms responsible for the observed toxicity. Crit Rev Toxicol 40:328–346

    Article  CAS  PubMed  Google Scholar 

  • Jones SW, Roberts RA, Robbins GR, Perry JL, Kai MP, Chen K, Bo T, Napier ME, Ting JP, DeSimone JM, Bear JE (2013) Nanoparticle clearance is governed by Th1/Th2 immunity and strain background. J Clin Invest 123:3061–3073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jovanovic B (2015) Critical review of public health regulations of titanium dioxide, a human food additive. Integr Environ Assess Manag 11:10–20

    Article  CAS  PubMed  Google Scholar 

  • Kanebratt KP, Andersson TB (2008) Evaluation of HepaRG cells as an in vitro model for human drug metabolism studies. Drug Metab Dispos 36:1444–1452

    Article  CAS  PubMed  Google Scholar 

  • Keller J, Wohlleben W, Ma-Hock L, Strauss V, Gröters S, Küttler K, Wiench K, Herden C, Oberdörster G, Van RB, Landsiedel R (2014) Time course of lung retention and toxicity of inhaled particles: short-term exposure to nano-Ceria. Arch Toxicol 88:2033–2059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim KT, Tanguay RL (2014) The role of chorion on toxicity of silver nanoparticles in the embryonic zebrafish assay. Environ Health Toxicol 29:e2014021

    Article  PubMed  PubMed Central  Google Scholar 

  • Klein CL, Comero S, Stahlmecke B, Romazanov J, Kuhlbusch TAJ, Van Doren E, De Temmermann P-J, Mast J, Wick P, Krug H, Locoro G, Hund-Rinke K, Kördel W, Friedrichs S, Maier G, Werner J, Linsinger T, Gawlik BM (2011) NM-300 silver. Characterisation, stability, homogeneity. Publications Office of the European Union, European Union

    Google Scholar 

  • Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163

    Article  CAS  PubMed  Google Scholar 

  • Landesmann B (2015) Protein alkylation leading to liver fibrosis.aop wiki, https://aopwiki.org/wiki/images/c/c0/Aop38-Snapshot-March2015.pdf. Accessed 7 Nov 2017

  • Landesmann B, Goumenou M, Munn S, Whelan M (2012) Description of prototype modes-of-action related to repeated dose toxicity. Publications Office of the European Union, European Union

    Google Scholar 

  • Lester E, Blood P, Denyer J, Giddings D, Azzopardi B, Poliakoff M (2006) Reaction engineering: the supercritical water hydrothermal synthesis of nano-particles. J Supercrit Fluid 37:209–214

    Article  CAS  Google Scholar 

  • Lester E, Tang SVY, Khlobystov A, Loczenski Rose V, Buttery L, Roberts CJ (2013) Producing nanotubes of biocompatible hydroxyapatite by continuous hydrothermal synthesis. Cryst Eng Comm 15:3256

    Article  CAS  Google Scholar 

  • Ling XB (2008) High throughput screening informatics. Comb Chem High Throughput Screen 11:249–257

    Article  CAS  PubMed  Google Scholar 

  • Liu R, Hassan T, Rallo R, Cohen Y (2013) HDAT: web-based high-throughput screening data analysis tools. Comput Sci Disc 6:014006

    Article  Google Scholar 

  • Lynch I, Weiss C, Valsami-Jones E (2014) A strategy for grouping of nanomaterials based on key physico-chemical descriptors as a basis for safer-by-design NMs. Nano Today 9:266–270

    Article  CAS  Google Scholar 

  • Marquardt C, Fritsch-Decker S, Al-Rawi M, Diabaté S, Weiss C (2017) Autophagy induced by silica nanoparticles protects RAW264.7 macrophages from cell death. Toxicology 379:40–47

    Article  CAS  PubMed  Google Scholar 

  • Menendez D, Inga A, Resnick MA (2009) The expanding universe of p53 targets. Nat Rev Cancer 9:724–737

    Article  CAS  PubMed  Google Scholar 

  • Mennecozzi M, Landesmann B, Harris GA, Liska R, Whelan M (2012) Hepatotoxicity screening taking a mode-of-action approach using HepaRG cells and HCA. ALTEX Proc WC8 1:193–204

    Google Scholar 

  • Morishige T, Yoshioka Y, Inakura H, Tanabe A, Narimatsu S, Yao X, Monobe Y, Imazawa T, Tsunoda S, Tsutsumi Y, Mukai Y, Okada N, Nakagawa S (2012) Suppression of nanosilica particle-induced inflammation by surface modification of the particles. Arch Toxicol 86:1297–1307

    Article  CAS  PubMed  Google Scholar 

  • Mülhopt S, Diabaté S, Krebs T, Weiss C, Paur HR (2009) Lung toxicity determination by in vitro exposure at the air-liquid interface with an integrated online dose measurement. J Phys 170:012008

    Google Scholar 

  • Nel A, Xia T, Meng H, Wang X, Lin S, Ji Z, Zhang H (2013) Nanomaterial toxicity testing in the 21st century: use of a predictive toxicological approach and high-throughput screening. Acc Chem Res 46:607–621

    Article  CAS  PubMed  Google Scholar 

  • OECD (2010) Series on the safety of manufactured nanomaterials No. 27. List of manufactured nanomaterials and list of endpoints for phase one of the sponsorship programme for the testing of manufactured nanomaterials: revision. Organization for Economic Co-operation and Development (OECD), Environment directorate, Paris

  • Ojea-Jimenez I, Urban P, Barahona F, Pedroni M, Capomaccio R, Ceccone G, Kinsner-Ovaskainen A, Rossi F, Gilliland D (2016) Highly flexible platform for tuning surface properties of silica nanoparticles and monitoring their biological interaction. ACS Appl Mater Interfaces 8:4838–4850

    Article  CAS  PubMed  Google Scholar 

  • Panas A, Marquardt C, Nalcaci O, Bockhorn H, Baumann W, Paur HR, Mülhopt S, Diabaté S, Weiss C (2013) Screening of different metal oxide nanoparticles reveals selective toxicity and inflammatory potential of silica nanoparticles in lung epithelial cells and macrophages. Nanotoxicology 7:259–273

    Article  CAS  PubMed  Google Scholar 

  • Panas A, Comouth A, Saathoff H, Leisner T, Al-Rawi M, Simon M, Seemann G, Dössel O, Mülhopt S, Paur HR, Fritsch-Decker S, Weiss C, Diabaté S (2014) Silica nanoparticles are less toxic to human lung cells when deposited at the air-liquid interface compared to conventional submerged exposure. Beilstein J Nanotechnol 5:1590–1602

    Article  PubMed  PubMed Central  Google Scholar 

  • Park EJ, Yi J, Chung KH, Ryu DY, Choi J, Park K (2008) Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells. Toxicol Lett 180:222–229

    Article  CAS  PubMed  Google Scholar 

  • Pele LC, Thoree V, Bruggraber SF, Koller D, Thompson RP, Lomer MC, Powell JJ (2015) Pharmaceutical/food grade titanium dioxide particles are absorbed into the bloodstream of human volunteers. Part Fibre Toxicol 12:26

    Article  PubMed  PubMed Central  Google Scholar 

  • Piret JP, Bondarenko OM, Boyles MSP, Himly M, Ribeiro AR, Benetti F, Smal C, Lima B, Potthoff A, Simion M, Dumortier E, Leite PEC, Balottin LB, Granjeiro JM, Ivask A, Kahru A, Radauer-Preiml I, Tischler U, Duschl A, Saout C, Anguissola S, Haase A, Jacobs A, Nelissen I, Misra SK, Toussaint O (2017) Pan-European inter-laboratory studies on a panel of in vitro cytotoxicity and pro-inflammation assays for nanoparticles. Arch Toxicol 91:2315–2330

    Article  CAS  PubMed  Google Scholar 

  • Ramuz O, Isnardon D, Devilard E, Charafe-Jauffret E, Hassoun J, Birg F, Xerri L (2003) Constitutive nuclear localization and initial cytoplasmic apoptotic activation of endogenous caspase-3 evidenced by confocal microscopy. Int J Exp Pathol 84:75–81

    Article  PubMed  PubMed Central  Google Scholar 

  • Rasmussen K, Mast J, De Temmerman PJ, Verleysen E, Waegeneers N, Van Steen F, Pizzolon JC, De Temmerman L, Van Doren E, Jensen KA, Birkedal R, Levin M, Nielsen SH, Koponen IK, Clausen PA, Kofoed-Sorensen V, Kembouche Y, Thieriet N, Spalla O, Guiot C, Rousset D, Witschger O, Bau S, Bianchi B, Motzkus C, Shivachev B, Dimova L, Nikolova R, Nihtianova D, Tarassov M, Petrov O, Bakardjieva S, Gilliland D, Pianella F, Ceccone G, Spampinato V, Cotogno G, Gibson N, Gaillard C, Mech A (2014) Titanium dioxide, NM-100, NM-101, NM-102, NM-103, NM-104, NM-105: characterisation and physico-chemical properties. Publications Office of the European Union, European Union

    Google Scholar 

  • Reidy B, Haase A, Luch A, Dawson KA, Lynch I (2013) Mechanisms of silver nanoparticle release, transformation and toxicity: a critical review of current knowledge and recommendations for future studies and applications. Materials 6:2295–2350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Röttgermann PJ, Alberola AP, Rädler JO (2014a) Cellular self-organization on micro-structured surfaces. Soft Matter 10:2397–2404

    Article  PubMed  Google Scholar 

  • Röttgermann PJ, Hertrich S, Berts I, Albert M, Segerer FJ, Moulin JF, Nickel B, Rädler JO (2014b) Cell motility on polyethylene glycol block copolymers correlates to fibronectin surface adsorption. Macromol Biosci 14:1755–1763

    Article  PubMed  Google Scholar 

  • Sayes CM, Wahi R, Kurian PA, Liu Y, West JL, Ausman KD, Warheit DB, Colvin VL (2006) Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol Sci 92:174–185

    Article  CAS  PubMed  Google Scholar 

  • Schoonen WGEJ, Westerink WMA, Van de Water FM, Jean HG (2013) High-throughput toxicity testing in drug development: aim, strategies, and novel trends. In: Steinberg P (ed) High-throughput screening methods in toxicity testing. Wiley, Hoboken, pp 33–75

    Chapter  Google Scholar 

  • Schreck I, Deigendesch U, Burkhardt B, Marko D, Weiss C (2012) The Alternaria mycotoxins alternariol and alternariol methyl ether induce cytochrome P450 1A1 and apoptosis in murine hepatoma cells dependent on the aryl hydrocarbon receptor. Arch Toxicol 86:625–632

    Article  CAS  PubMed  Google Scholar 

  • Sha B, Gao W, Cui X, Wang L, Xu F (2015) The potential health challenges of TiO2 nanomaterials. J Appl Toxicol 35:1086–1101

    Article  CAS  PubMed  Google Scholar 

  • Shi Y, Wang F, He J, Yadav S, Wang H (2010) Titanium dioxide nanoparticles cause apoptosis in BEAS-2B cells through the caspase 8/t-Bid-independent mitochondrial pathway. Toxicol Lett 196:21–27

    Article  CAS  PubMed  Google Scholar 

  • Shi H, Magaye R, Castranova V, Zhao J (2013) Titanium dioxide nanoparticles: a review of current toxicological data. Part Fibre Toxicol 10:15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh C, Friedrichs S, Levin M, Birkedal R, Jensen KA, Pojana G, Wohlleben W, Schulte S, Wiench K, Turney T, Koulaeva O, Marshall D, Hund-Rinke K, Kördel W, Van Doren E, De Temmermann PJ, Abi Daoud Francisco M, Mast J, Gibson N, Koeber R, Linsinger T, Klein CL (2011) Zinc oxide NM-110, NM-111, NM-112, NM-113. Characterisation and test item preparation. Publications Office of the European Union, European Union

    Google Scholar 

  • Singh C, Friedrichs S, Ceccone G, Gibson N, Jensen KA, Levin M, Infante HG, Carlander D, Rasmussen K (2014) Cerium dioxide, NM-211, NM-212, NM-213. Characterisation and test item preparation. Publications Office of the European Union, European Union

    Google Scholar 

  • Stern ST, Adiseshaiah PP, Christ RM (2012) Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Part Fibre Toxicol 9:20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tralau T, Oelgeschlager M, Gurtler R, Heinemeyer G, Herzler M, Hofer T, Itter H, Kuhl T, Lange N, Lorenz N, Muller-Graf C, Pabel U, Pirow R, Ritz V, Schafft H, Schneider H, Schulz T, Schumacher D, Zellmer S, Fleur-Bol G, Greiner M, Lahrssen-Wiederholt M, Lampen A, Luch A, Schonfelder G, Solecki R, Wittkowski R, Hensel A (2015) Regulatory toxicology in the twenty-first century: challenges, perspectives and possible solutions. Arch Toxicol 89:823–850

    Article  CAS  PubMed  Google Scholar 

  • Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40

    Article  CAS  PubMed  Google Scholar 

  • Wang F, Bexiga MG, Anguissola S, Boya P, Simpson JC, Salvati A, Dawson KA (2013a) Time resolved study of cell death mechanisms induced by amine-modified polystyrene nanoparticles. Nanoscale 5:10868–10876

    Article  CAS  PubMed  Google Scholar 

  • Wang F, Yu L, Monopoli MP, Sandin P, Mahon E, Salvati A, Dawson KA (2013b) The biomolecular corona is retained during nanoparticle uptake and protects the cells from the damage induced by cationic nanoparticles until degraded in the lysosomes. Nanomedicine 9:1159–1168

    Article  CAS  PubMed  Google Scholar 

  • Weir A, Westerhoff P, Fabricius L, Hristovski K, von Goetz N (2012) Titanium dioxide nanoparticles in food and personal care products. Environ Sci Technol 46:2242–2250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Westerink WMA, Stevenson JCR, Horbach GJ, Van de Water FM, Van de Waart B, Schoonen WGEJ (2013) Genotoxicity and carcinogenicity: regulatory and novel test methods. In: Steinberg P (ed) High-throughput screening methods in toxicity testing. Wiley, Hoboken, pp 233–269

    Chapter  Google Scholar 

  • Wu W, Bromberg PA, Samet JM (2013) Zinc ions as effectors of environmental oxidative lung injury. Free Radic Biol Med 65:57–69

    Article  CAS  PubMed  Google Scholar 

  • Xia T, Kovochich M, Liong M, Zink JI, Nel AE (2008) Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways. ACS Nano 2:85–96

    Article  CAS  PubMed  Google Scholar 

  • Yamashita K, Yoshioka Y, Higashisaka K, Mimura K, Morishita Y, Nozaki M, Yoshida T, Ogura T, Nabeshi H, Nagano K, Abe Y, Kamada H, Monobe Y, Imazawa T, Aoshima H, Shishido K, Kawai Y, Mayumi T, Tsunoda S, Itoh N, Yoshikawa T, Yanagihara I, Saito S, Tsutsumi Y (2011) Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. Nat Nanotechnol 6:321–328

    Article  CAS  PubMed  Google Scholar 

  • Yoon HJ, Cha BS (2014) Pathogenesis and therapeutic approaches for non-alcoholic fatty liver disease. World J Hepatol 6:800–811

    Article  PubMed  PubMed Central  Google Scholar 

  • Yu F, Chen Z, Wang B, Jin Z, Hou Y, Ma S, Liu X (2016) The role of lysosome in cell death regulation. Tumour Biol 37:1427–1436

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y, Howe JL, Yu Z, Leong DT, Chu JJ, Loo JS, Ng KW (2013) Exposure to titanium dioxide nanoparticles induces autophagy in primary human keratinocytes. Small 9:387–392

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge support from the European Commission’s 7th Framework Programme project NanoMILE (Contract No. NMP4-LA-2013-310451).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carsten Weiss.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 689 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hansjosten, I., Rapp, J., Reiner, L. et al. Microscopy-based high-throughput assays enable multi-parametric analysis to assess adverse effects of nanomaterials in various cell lines. Arch Toxicol 92, 633–649 (2018). https://doi.org/10.1007/s00204-017-2106-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-017-2106-7

Keywords

Navigation