Skip to main content
SpringerLink
Log in

Cerium Oxide Nanoparticles are More Toxic than Equimolar Bulk Cerium Oxide in Caenorhabditis elegans

  • Published:
Archives of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

Engineered cerium oxide nanoparticles (CeO2 NPs) are widely used in biomedical and engineering manufacturing industries. Previous research has shown the ability of CeO2 NPs to act as a redox catalyst, suggesting potential to both induce and alleviate oxidative stress in organisms. In this study, Caenorhabditis elegans and zebrafish (Danio rerio) were dosed with commercially available CeO2 NPs. Non-nano cerium oxide powder (CeO2) was used as a positive control for cerium toxicity. CeO2 NPs suspended in standard United States Environmental Protection Agency reconstituted moderately hard water, used to culture the C. elegans, quickly formed large polydisperse aggregates. Dosing solutions were renewed daily for 3 days. Exposure of wild-type nematodes resulted in dose-dependent growth inhibition detected for all 3 days (p < 0.0001). Non-nano CeO2 also caused significant growth inhibition (p < 0.0001), but the scale of inhibition was less at equivalent mass exposures compared with CeO2 NP exposure. Some metal and oxidative stress-sensitive mutant nematode strains showed mildly altered growth relative to the wild-type when dosed with 5 mg/L CeO2 NPs on days 2 and 3, thus providing weak evidence for a role for oxidative stress or metal sensitivity in CeO2 NP toxicity. Zebrafish microinjected with CeO2 NPs or CeO2 did not exhibit increased gross developmental defects compared with controls. Hyperspectral imaging showed that CeO2 NPs were ingested but not detectable inside the cells of C. elegans. Growth inhibition observed in C. elegans may be explained at least in part by a non-specific inhibition of feeding caused by CeO2 NPs aggregating around bacterial food and/or inside the gut tract.

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

Access this article

Log in via an institution

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

  • Bach U, Corr D, Lupo D, Pichot F, Ryan M (2002) Nanomaterials-based electrochromics for paper-quality displays. Adv Mater 14(11):845–848

    Article  CAS  Google Scholar 

  • Billiard SM, Timme-Laragy AR, Wassenberg DW, Cockman C, Di Giulio RT (2006) The role of the aryl hydrocarbon receptor pathway in mediating synergistic developmental toxicity of polycyclic aromatic hydrocarbons to zebrafish. Toxicol Sci 92(2):526–536

    Article  CAS  Google Scholar 

  • Choi JE, Kim S, Ahn JH, Youn P, Kang JS, Park K et al (2010) Induction of oxidative stress and apoptosis by silver nanoparticles in the liver of adult zebrafish. Aquat Toxicol 100(2):151–159

    Article  CAS  Google Scholar 

  • Corma A, Atienzar P, García H, Chane-Ching J-V (2004) Hierarchically mesostructured doped CeO2 with potential for solar-cell use. Nature Mater 3(6):394–397

    Article  CAS  Google Scholar 

  • Croteau DL, DellaVecchia MJ, Perera L, Van Houten B (2008) Cooperative damage recognition by UvrA and UvrB: identification of UvrA residues that mediate DNA binding. DNA Repair (Amst.) 7:392–404

    Article  CAS  Google Scholar 

  • Das M, Patil S, Bhargavaa N, Kanga J-F, Riedela LM, Sealb S et al (2007) Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. Biomaterials 28(10):1918–1925

    Article  CAS  Google Scholar 

  • Di Giulio RT, Meyer JN (2008) Reactive oxygen species and oxidative stress. In: Di Giulio RT, Hinton DE (eds) The toxicology of fishes. CRC Press, Boca Raton, pp 273–324

    Chapter  Google Scholar 

  • Dingley S, Polyak E, Lightfoot R, Ostrovskya J, Raoa M, Grecob T et al (2010) Mitochondrial respiratory chain dysfunction variably increases oxidant stress in Caenorhabditis elegans. Mitochondrion 10(2):125–136

    Article  CAS  Google Scholar 

  • Eom HJ, Choi J (2009) Oxidative stress of CeO(2) nanoparticles via p38–Nrf–2 signaling pathway in human bronchial epithelial cell, Beas-2B. Toxicol Lett 187(2):77–83

    Article  CAS  Google Scholar 

  • Freedman JH, Slice LW, Dixon D, Fire A, Rubin CS (1993) The novel metallothionein genes of Caenorhabditis elegans—Structural organization and inducible, cell-specific expression. J Biol Chem 268(4):2554–2564

    CAS  Google Scholar 

  • Gorensek M, Recetj P (2007) Nanosilver functionalized cotton fabric. Textile Res J 77(3):138–141

    Article  CAS  Google Scholar 

  • Heckert EG, Karakoti AS, Seal S, Self WT (2008) The role of cerium redox state in the SOD mimetic activity of nanoceria. Biomaterials 29(18):2705–2709

    Article  CAS  Google Scholar 

  • Hughes SL, Bundy JG, Want EJ, Kille P, Stürzenbaum SR (2009) The metabolomic responses of Caenorhabditis elegans to cadmium are largely independent of metallothionein status, but dominated by changes in cystathionine and phytochelatins. J Proteome Res 8(7):3512–3519

    Article  CAS  Google Scholar 

  • Hunter T, Bannister WH, Hunter GJ (1997) Cloning, expression, and characterization of two manganese superoxide dismutases from Caenorhabditis elegans. J Biol Chem 272(45):28652–28659

    Article  CAS  Google Scholar 

  • Hunter SE, Gustafson MA, Margillo KM, Lee SA, Ryde IT, Meyer JN (2012) In vivo repair of alkylating and oxidative DNA damage in the mitochondrial and nuclear genomes of wild-type and glycosylase-deficient Caenorhabditis elegans. DNA Repair 11(11):857–863

    Article  CAS  Google Scholar 

  • Johnston BD, Scown TM, Moger J, Cumberland SA, Baalousha M, Linge K et al (2010) Bioavailability of nanoscale metal oxides TiO(2), CeO(2), and ZnO to fish. Environ Sci Technol 44(3):1144–1151

    Article  CAS  Google Scholar 

  • Lin W, Huang YW, Zhou X-D, Ma Y (2006) Toxicity of cerium oxide nanoparticles in human lung cancer cells. Int J Toxicol 25(6):451–457

    Article  CAS  Google Scholar 

  • Matson CW, Timme-Laragy AR, Di Giulio RT (2008) Fluoranthene, but not benzo[a]pyrene, interacts with hypoxia resulting in pericardial effusion and lordosis in developing zebrafish. Chemosphere 74(1):149–154

    Article  CAS  Google Scholar 

  • McWilliams A (2010) Nanotechnology: a realistic market assessment. BCC Research, Wellesley

    Google Scholar 

  • Meyer JN, Boyd WA, Azzam GA, Haugen AC, Freedman JH, Van Houten B (2007) Decline of nucleotide excision repair capacity in aging Caenorhabditis elegans. Genome Biol 8(5):R70

    Article  Google Scholar 

  • Meyer JN, Lord CA, Yang XY, Turner EA, Badireddy AR, Marinakos SM et al (2010) Intracellular uptake and associated toxicity of silver nanoparticles in Caenorhabditis elegans. Aquat Toxicol 100(2):140–150

    Article  CAS  Google Scholar 

  • Murray EP, Tsai T, Barnett SA (1999) A direct-methane fuel cell with a ceria-based anode. Nature 400(6745):649–651

    Article  CAS  Google Scholar 

  • Niu JL, Azfer A, Rogers LM, Wang X, Kolattukudy PE (2007) Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. Cardiovasc Res 73(3):549–559

    Article  CAS  Google Scholar 

  • Nohynek GJ, Lademann J, Ribaud C, Roberts MS (2007) Grey goo on the skin? Nanotechnology, cosmetic and sunscreen safety. Crit Rev Toxicol 37(3):251–277

    Article  CAS  Google Scholar 

  • Park B, Donaldson K, Duffin R, Tran L, Kelly F, Mudway I et al (2008a) Hazard and risk assessment of a nanoparticulate cerium oxide-based diesel fuel additive—A case study. Inhal Toxicol 20(6):547–566

    Article  CAS  Google Scholar 

  • Park EJ, Choi J, Park Y-K, Park K (2008b) Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells. Toxicology 245(1–2):90–100

    Article  CAS  Google Scholar 

  • Roh JY, Park YK, Park K, Choi J (2010) Ecotoxicological investigation of CeO2 and TiO2 nanoparticles on the soil nematode Caenorhabditis elegans using gene expression, growth, fertility, and survival as endpoints. Environ Toxicol Pharmacol 29(2):167–172

    Article  CAS  Google Scholar 

  • Swain SC, Keusekotten K, Baumeister R, Stürzenbaum SR (2004) C. elegans metallothioneins: new insights into the phenotypic effects of cadmium toxicosis. J Mol Biol 341(4):951–959

    Article  CAS  Google Scholar 

  • Tiede K, Hassellov M, Breitbarth E, Chaudhry Q, Boxalla ABA (2009) Considerations for environmental fate and ecotoxicity testing to support environmental risk assessments for engineered nanoparticles. J Chromatogr A 1216(3):503–509

    Article  CAS  Google Scholar 

  • Timme-Laragy AR, Van Tiem LA, Linney EA, Di Giulio RT (2009) Antioxidant responses and NRF2 in synergistic developmental toxicity of PAHs in zebrafish. Toxicol Sci 109(2):217–227

    Article  CAS  Google Scholar 

  • USEPA (2002) Methods for measuring the acute toxicity of effluents and receiving waters to freshwater and marine organisms. USEPA, Washington, DC

    Google Scholar 

  • Van Hoecke K, Quik JT, Mankiewicz-Boczek J, De Schamphelaere KAC, Elsaesser A, Van der Meeren P et al (2009) Fate and effects of CeO2 nanoparticles in aquatic ecotoxicity tests. Environ Sci Technol 43(12):4537–4546

    Article  Google Scholar 

  • Van Tiem LA, Di Giulio RT (2011) AHR2 knockdown prevents PAH-mediated cardiac toxicity and XRE- and ARE-associated gene induction in zebrafish (Danio rerio). Toxicol Appl Pharmacol 254(3):280–287

    Article  Google Scholar 

  • Vatamaniuk OK, Bucher EA, Ward JT, Rea PA (2001) A new pathway for heavy metal detoxification in animals—Phytochelatin synthase is required for cadmium tolerance in Caenorhabditis elegans. J Biol Chem 276(24):20817–20820

    Article  CAS  Google Scholar 

  • Wang R, Crozier PA, Sharma R, Adams JB (2008) Measuring the redox activity of individual catalytic nanoparticles in cerium-based oxides. Nano Lett 8(3):962–967

    Article  CAS  Google Scholar 

  • Xia T, Kovochich M, Brant J, Hotze M, Sempf J, Oberley T et al (2006) Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett 6(8):1794–1807

    Article  CAS  Google Scholar 

  • Xia T, Kovochich M, Liong M, Mädler L, Gilbert B, Shi H et al (2008) Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. ACS Nano 2(10):2121–2134

    Article  CAS  Google Scholar 

  • Yang X, Gondikas AP, Marinakos SM, Auffan M, Liu J, Hsu-Kim H et al (2012) Mechanism of silver nanoparticle toxicity is dependent on dissolved silver and surface coating in Caenorhabditis elegans. Environ Sci Technol 46(2):1119–1127

    Article  CAS  Google Scholar 

  • Zhang HF, He XA, Zhang Z, Zhang P, Li Y, Ma Y et al (2011) Nano-CeO2 exhibits adverse effects at environmental relevant concentrations. Environ Sci Technol 45(8):3725–3730

    Article  CAS  Google Scholar 

  • Zheng XC, Zhang XL, Wang X, Wang S, Wub S (2005) Preparation and characterization of CuO/CeO2 catalysts and their applications in low-temperature CO oxidation. Appl catal A Gen 295(2):142–149

    Article  CAS  Google Scholar 

  • Zhou XD, Huebner W, Anderson HU (2003) Processing of nanometer-scale CeO2 particles. Chem Mater 15(2):378–382

    Article  CAS  Google Scholar 

  • Zhu XS, Zhu L, Yan Y, Duan Z, Chen W, Alvarez PJJ (2007) Developmental toxicity in zebrafish (Danio rerio) embryos after exposure to manufactured nanomaterials: buckminsterfullerene aggregates (nC(60)) and fullerol. Environ Toxicol Chem 26(5):976–979

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Science Foundation (NSF) and the USEPA under NSF Cooperative Agreement No. EF-0830093, Center for the Environmental Implications of NanoTechnology. Any opinions, findings, conclusions, or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the NSF or the USEPA. This work has not been subjected to USEPA review, and no official endorsement should be inferred. All strains except JF23 were originally provided by the C. elegans Reverse Genetics Core Facility at the University of British Colombia, which is part of the International C. elegans Gene Knockout Consortium and is supported by the National Institute of Health—Office of Research Infrastructure Programs (Grant No. P40 OD010440). We gratefully acknowledge Elena Turner, Xinyu Yang, and Axel Berky for experimental assistance.

Author information

Authors and Affiliations

  1. Nicholas School of the Environment, Duke University, P.O. 90328, Durham, NC, 27708-0328, USA

    M. C. Arnold, R. T. Di Giulio & J. N. Meyer

  2. Pratt School of Engineering, Duke University, Durham, NC, 27708, USA

    A. R. Badireddy & M. R. Wiesner

Authors
  1. M. C. Arnold
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. R. Badireddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. R. Wiesner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. T. Di Giulio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. N. Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. N. Meyer.

Electronic supplementary material

Below is the link to the electronic supplementary material.

244_2013_9905_MOESM1_ESM.jpg

Online Resource 1. Soluble cerium (mg/L) in supernatant from CeO2 NP dosing solutions after 2 h ultracentrifugation (273865 x g) over three days. (JPG 421 kb)

244_2013_9905_MOESM2_ESM.jpg

Online Resource 2. Growth of N2 and sod3 worms treated with CeO2 NPs or H2O2. Asterisks indicate P<0.0001 as determined by Mann-Whitney U-test. (JPG 664 kb)

Online Resource 3-4. (DOCX 27 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arnold, M.C., Badireddy, A.R., Wiesner, M.R. et al. Cerium Oxide Nanoparticles are More Toxic than Equimolar Bulk Cerium Oxide in Caenorhabditis elegans . Arch Environ Contam Toxicol 65, 224–233 (2013). https://doi.org/10.1007/s00244-013-9905-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00244-013-9905-5

Keywords

Search

Navigation