Skip to main content
Log in

Human intestinal epithelial cells exhibit a cellular response indicating a potential toxicity upon exposure to hematite nanoparticles

  • Original Research
  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

This study examined the effects of different-sized nanoparticles on potential cytotoxicity in intestinal epithelia. Three sizes of hematite nanoparticles were used for the study at a 10 ppm concentration: 17, 53, and, 100 nm. Results indicate that, of the hematite nanoparticles tested, 17 nm was more toxic to the epithelial integrity than 53 or 100 nm. In addition, the epithelial integrity was affected by disruption of epithelial structures such as apical microvilli, and by disruption of the cell–cell junctions leading to reduction in transepithelial electrical resistance measurements (TEER). The drop in TEER was caused by disruption of the adhering junctions not by cell death, as determined by immunocytochemistry, and by using a cell viability assay. Epithelial integrity was also affected at the molecular level as shown by differential expression of genes related to cell junction maintenance, which was assessed by microarray analysis. In conclusion, the 17- and 100-nm hematite nanoparticles caused significant structural changes in the epithelium but not the 53 nm nanoparticles. Also, different-sized hematite nanoparticles each had different effects both at the cellular level and genetic level.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

HNPs:

Hematite nanoparticles

TEER:

Transepithelial electrical resistance

References

  • Adams LK, Lyon DY, McIntosh A, Alvarez PJ. Comparative toxicity of nano-scale TiO2, SiO2 and ZnO water suspensions. Water Sci Technol. 2006;54:327–34.

    Article  PubMed  CAS  Google Scholar 

  • Barth AI, Näthke IS, Nelson WJ. Cadherins, catenins and APC protein: interplay between cytoskeletal complexes and signaling pathways. Curr Opin Cell Biol. 1997;5:683–90.

    Article  Google Scholar 

  • Bauer H, Zweimueller-Mayer J, Steinbacher P, Lametschwandtner A, Bauer HC. The dual role of zonula occludens (ZO) proteins. J Biomed Biotechnol. 2010; 402593.

  • Behrens J. Cadherins and catenins: role in signal transduction and tumor progression. Cancer Metastasis Rev. 1999;18:15–30.

    Article  PubMed  CAS  Google Scholar 

  • Benn TM, Westerhoff P. Nanoparticle silver released into water from commercially available sock fabrics. Environ Sci Technol. 2008;42:4133–9.

    Article  PubMed  CAS  Google Scholar 

  • Butz S, Stappert J, Weissig H, Kemler R. Plakoglobin and beta-catenin: distinct but closely related. Science. 1992;257:1142–4.

    Article  PubMed  CAS  Google Scholar 

  • Cadigan KM, Nusse R. Wnt signaling: a common theme in animal development. Genes Dev. 1997;11:3286–305.

    Article  PubMed  CAS  Google Scholar 

  • Capco DG, Penman S. Mitotic architecture of the cell: the filament networks of the nucleus and cytoplasm. J Cell Biol. 1983;96:896–906.

    Article  PubMed  CAS  Google Scholar 

  • Carlson C, Hussain SM, Schrand AM, Braydich-Stolle LK, Hess KL, Jones RL, et al. Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. J Phys Chem B. 2008;43:13608–19.

    Article  Google Scholar 

  • Cowin P, Kapprell HP, Franke WW, Tamkun J, Hynes RO. Plakoglobin: a protein common to different kinds of intercellular adhering junctions. Cell. 1986;26:1063–73.

    Article  Google Scholar 

  • Chen L, Yokel RA, Hennig B, Toborek M. Manufactured aluminum oxide nanoparticles decrease expression of tight junction proteins in brain vasculature. J Neuroimmune Pharmacol. 2008;4:286–95.

    Article  Google Scholar 

  • Chithrani BD, Ghazani AA, Chan WC. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 2006;4:662–8.

    Article  Google Scholar 

  • Dechsakulthorn F, Hayes A, Bakand S, Joeng L, Winder C. In vitro cytotoxicity assessment of selected nanoparticles using human skin fibroblasts. Proc. 6th World Congress on Alternatives & Animal Use in the Life Sciences. 2007; 14: 397-400.

  • Donaldson K, Stone V, Gilmour PS, Brown DM, MacNee W. Ultrafine particles: mechanisms of lung injury. Phil Trans Roy Soc London Series. 2000;358:2741–9.

    Article  CAS  Google Scholar 

  • Georgiadis A, Tschernutter M, Bainbridge JW, Balaggan KS, Mowat F, West EL, et al. The tight junction associated signalling proteins ZO-1 and ZONAB regulate retinal pigment epithelium homeostasis in mice. PLoS One. 2010;5:e15730.

    Article  PubMed  CAS  Google Scholar 

  • Hancock JT. Aspects of cellular signaling. In: Cell signalling. New York: Oxford University Press; 2010. p. 4–7.

    Google Scholar 

  • Jeng HA, Swanson J. Toxicity of metal oxide nanoparticles in mammalian cells. J Environ Sci Health, Part A: Tox Hazard Subst Environ Eng. 2006;41:2699–711.

    Article  CAS  Google Scholar 

  • Karlsson HL, Cronholm P, Gustafsson J, Moller L. Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. Chem Res Toxicol. 2008;21:1726–32.

    Article  PubMed  CAS  Google Scholar 

  • Kim IS, Baek M, Choi SJ. Comparative cytotoxicity of Al2O3, CeO2, TiO2 and ZnO nanoparticles to human lung cells. J Nanosci Nanotech. 2010;10:3453–8.

    Article  CAS  Google Scholar 

  • Koeneman BA, Zhang Y, Westerhoff P, Chen Y, Crittenden JC, Capco DG. Experimental approach for an in vitro toxicity assay with non-aggregated quantum dots. Toxicol In Vitro. 2009;5:955–62.

    Article  Google Scholar 

  • Koeneman BA, Zhang Y, Westerhoff P, Chen Y, Crittenden JC, Capco DG. Toxicity and cellular responses of intestinal cells exposed to titanium dioxide. Cell Biol Toxicol. 2010;26:225–38.

    Article  PubMed  CAS  Google Scholar 

  • Lam CW, James JT, McCluskey R, Hunter RL. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci. 2004;77:126–34.

    Article  PubMed  CAS  Google Scholar 

  • Lange K. Fundamental role of microvilli in the main functions of differentiated cells: outline of a universal regulating and signaling system at the cell periphery. J Cell Physiol. 2011;4:896–927.

    Article  Google Scholar 

  • Lewinski N, Colvin V, Drezek R. Cytotoxicity of nanoparticles. Small. 2008;4:26–49.

    Article  PubMed  CAS  Google Scholar 

  • Liew JLK, Chow VTK. Microarray and real-time RT-PCR analyses of a novel set of differentially expressed human genes in ECV304 endothelial-like cells infected with dengue virus type 2. J Virol Meth. 2006;131:47–57.

    Article  CAS  Google Scholar 

  • Marks F. The “Brain of the Cell”: data processing by protein networks. In: Marks F, Klingmuller U, Muller-Decker K, editors. Cellular signal processing: an introduction to the molecular mechanisms of signal transduction. New York: Garland Science, Taylor and Francis; 2009. p. 1–7.

    Google Scholar 

  • Mohapatra M, Anand S. Synthesis and applications of nano-structured iron oxides/hydroxides-a review. Int J Eng Sci Technol. 2010;2:127–46.

    Google Scholar 

  • Nel A, Xia T, Mädler L, Li N. Toxic potential of materials at the nanolevel. Science. 2006;311:622–7.

    Article  PubMed  CAS  Google Scholar 

  • Oberdörster G. Toxicology of ultrafine particles: in vivo studies. Phil Trans Roy Soc London Series. 2000;358:2719–40.

    Article  Google Scholar 

  • Oberdörster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, et al. Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Particle and Fibre Toxicology. 2005;2:8.

    Article  PubMed  Google Scholar 

  • Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R, Lunts A, et al. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health A. 2002;65:1531–43.

    Article  PubMed  Google Scholar 

  • Oberdörster G, Utell MJ. Ultrafine particles in the urban air: to the respiratory tract—and beyond? Environ Health Perspect. 2002;110:A440–1.

    Article  PubMed  Google Scholar 

  • Peterson MD, Mooseker MS. Characterization of the enterocyte-like brush border cytoskeleton of the C2BBe clones of the human intestinal cell line, Caco-2. J Cell Sci. 1992;102:581–600.

    PubMed  CAS  Google Scholar 

  • Peterson MD, Bement WM, Mooseker MS. An in vitro model for the analysis of intestinal brush border assembly. II. Changes in expression and localization of brush border proteins during cell contact-induced brush border assembly in Caco-2BBe cells. J Cell Sci. 1993;105:461–72.

    PubMed  CAS  Google Scholar 

  • Peterson MD, Mooseker MS. An in vitro model for the analysis of intestinal brush border assembly. I. Ultrastructural analysis of cell contact-induced brush border assembly in Caco-2BBe cells. J Cell Sci. 1993;105:445–60.

    PubMed  Google Scholar 

  • Ponsuksili S, Murani E, Phatsara C, Schwerin M, Schellander K, Wimmers K. Expression quantitative trait loci analysis of genes in porcine muscle by quantitative real-time RT-PCR compared to microarray data. Heredity. 2010;105:309–17.

    Article  PubMed  CAS  Google Scholar 

  • Prabhu BM, Ali SF, Murdock RC, Hussain SM, Srivatsan M. Copper nanoparticles exert size and concentration dependent toxicity on somatosensory neurons of rat. Nanotoxicology. 2010;4:150–60.

    Article  PubMed  CAS  Google Scholar 

  • Rico CM, Majumdar S, Duarte-Gardea M, Peralta-Videa JR, Gardea-Torresdey JL. Interaction of nanoparticles with edible plants and their possible implications in the food chain. J Agric Food Chem. 2011;59:3485–98.

    Article  PubMed  CAS  Google Scholar 

  • Salata O. Applications of nanoparticles in biology and medicine. J Nanobiotechnology. 2004;2:3.

    Article  PubMed  Google Scholar 

  • Sbarbati A, Osculati F. A new fate for old cells: brush cells and related elements. J Anat. 2005;206:349–58.

    Article  PubMed  CAS  Google Scholar 

  • Slotkin JR, Chakrabarti L, Dai HN, Carney RS, Hirata T, Bregman BS, et al. In vivo quantum dot labeling of mammalian stem and progenitor cells. Dev Dyn. 2007;236:3393–401.

    Article  PubMed  CAS  Google Scholar 

  • Stumm W, Morgan JJ. Aquatic chemistry. 3rd ed. New York: Wiley; 1996.

    Google Scholar 

  • Sun H, Zhang X, Zhang Z, Chen Y, Crittenden JC. Influence of titanium dioxide nanoparticles on speciation and bioavailability of arsenite. Environ Pollut. 2009;157:1165–70.

    Article  PubMed  CAS  Google Scholar 

  • Swanson JA, Lee M, Knapp PE. Cellular dimensions affecting the nucleocytoplasmic volume ratio. J Cell Biol. 1991;115:941–8.

    Article  PubMed  CAS  Google Scholar 

  • Schwarz SM, Gallicano IG, McGaughey RW, Capco DG. A role for intermediate filaments in the establishment of the primitive epithelia during mammalian embryogenesis. Mech Dev. 1995;53:305–21.

    Article  PubMed  CAS  Google Scholar 

  • Tinkle SS, Antonini JM, Rich BA, Roberts JR, Salmen R, DePree K, et al. Skin as a route of exposure and sensitization in chronic beryllium disease. Environ Health Perspect. 2003;9:1202–8.

    Article  Google Scholar 

  • Thubagere A, Reinhard BM. Nanoparticle-induced apoptosis propagates through hydrogen-peroxide-mediated bystander killing: insights from a human intestinal epithelium in vitro model. ACS Nano. 2010;4:3611–22.

    Article  PubMed  CAS  Google Scholar 

  • Tümer Z, Croucher PJ, Jensen LR, Hampe J, Hansen C, Kalscheuer V, Ropers HH, Tommerup N, Schreiber S. Genomic structure, chromosome mapping and expression analysis of the human AVIL gene, and its exclusion as a candidate for locus for inflammatory bowel disease at 12q13-14 (IBD2). Gene. 2002;288:179–85.

    Google Scholar 

  • Wang B, Feng W, Zhu M, Wang Y, Wang M, Gu Y, et al. Neurotoxicity of low-dose repeatedly intranasal instillation of nano- and submicron-sized ferric oxide particles in mice. J Nanopart Res. 2009;8:9452–6.

    Google Scholar 

  • Yan H, Zhang B. In vitro cytotoxicity of monodispersed hematite nanoparticles on Hek 293 cells. Mater Lett. 2011;65:815–7.

    Article  CAS  Google Scholar 

  • Zahraoui A, Joberty G, Arpin M, Fontaine JJ, Hellio R, Tavitian A, et al. A small rab GTPase is distributed in cytoplasmic vesicles in non polarized cells but colocalizes with the tight junction marker ZO-1 in polarized epithelial cells. J Cell Biol. 1994;124:101–15.

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Sun H, Zhang Z, Niu Q, Chen Y, Crittenden JC. Enhanced bioaccumulation of cadmium in carp in the presence of titanium dioxide nanoparticles. Chemosphere. 2007a;67:160–6.

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Sun H, Zhang Z, Niu Q, Chen Y, Crittenden JC. Enhanced accumulation of arsenic in carp in the presence of titanium dioxide nanoparticles. Water Air Soil Pollut. 2007b;178:245–54.

    Article  Google Scholar 

  • Zhang Y, Chen Y, Westerhoff P, Crittenden JC. Stability and removal of water soluble CdTe quantum dots in water. Environ Sci Technol. 2008a;42:321–5.

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Chen Y, Westerhoff P, Hristovski K, Crittenden JC. Stability of commercial metal oxide nanoparticles in water. Water Res. 2008b;42:2204–12.

    Article  PubMed  CAS  Google Scholar 

  • Zhang W, Kalive M, Capco DG, Chen Y. Adsorption of hematite nanoparticles onto Caco-2 cells and the cellular impairments: effect of particle size. Nanotechnology. 2010;21:355103.

    Article  PubMed  Google Scholar 

  • Zhang W, Rittmann B, Chen Y. Size effects on adsorption of hematite nanoparticles on E. coli cells. Environ Sci Technol. 2011;45:2172–8.

    Article  PubMed  CAS  Google Scholar 

  • Zhou Y, Yokel RA. The chemical species of aluminum influences its paracellular flux across and uptake into Caco-2 cells, a model of gastrointestinal absorption. Toxicol Sci. 2005;87:15–26.

    Article  PubMed  CAS  Google Scholar 

  • Zhu X, Zhu L, Lang Y, Chen Y. Oxidative stress and growth inhibition by nC60 on fish. Environ Toxicol Chem. 2008;24:1.

    CAS  Google Scholar 

  • Zhu X, Zhu L, Chen Y, Tian S. Acute toxicities of six manufactured nanomaterial suspensions to Daphnia magna. J Nanopart Res. 2009;11:67–75.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We wish to thank the W.M. Keck Bioimaging Laboratory, the Electron Microscope Laboratory, and the Molecular Biology Laboratory at the School of Life Sciences, Arizona State University. This research was supported by a grant from the Environmental Protection Agency (EPA) USA, grant numbers: EPA-G2007-STAR-R1 and RD-83385601. The authors wish to state that there is no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yongsheng Chen or David G. Capco.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kalive, M., Zhang, W., Chen, Y. et al. Human intestinal epithelial cells exhibit a cellular response indicating a potential toxicity upon exposure to hematite nanoparticles. Cell Biol Toxicol 28, 343–368 (2012). https://doi.org/10.1007/s10565-012-9229-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-012-9229-7

Keywords

Navigation