Toxicity and cellular responses of intestinal cells exposed to titanium dioxide

Brian A. Koeneman, Yang Zhang, Paul Westerhoff, Yongsheng Chen, John C. Crittenden, David Capco

Research output: Contribution to journalArticlepeer-review

187 Scopus citations


The increasing use of nanomaterials in healthcare and industrial products heightens the possibility of their ingestion by humans, other mammals, and fish. While toxicity of many nanomaterials has recently been studied, reports of non-lethal effects of nanomaterials remain ill-defined. This study investigates possible pathways by which nanoparticles, titanium dioxide (TiO2), could cross the epithelium layer by employing both toxicity and mechanistic studies. This study provides evidence that at 10 μg/mL and above, TiO 2 nanoparticles cross the epithelial lining of the intestinal model by transcytosis, albeit at low levels. TiO2 was able to penetrate into and through the cells without disrupting junctional complexes, as measured by γ-catenin. To monitor the epithelial integrity, transepithelial electrical resistance (TEER) was employed and determined low concentrations (10 or 100 μg/mL) of TiO2 do not disrupt epithelial integrity. Live/dead analysis results did not show cell death after exposure to TiO 2. In addition, at 10 μg/mL (and above) TiO2 nanoparticles begin alteration of both microvillar organization on the apical surface of the epithelium as well as induce a rise in intracellular-free calcium. The latter is a mechanism cells use to respond to extracellular stimuli and may be linked to the alteration of the apical microvilli. Although TiO 2 does not show cell death, the implication of other, non-lethal, effects could lead to undesired outcomes (i.e., disease, malnutrition, shortened life span, etc.).

Original languageEnglish (US)
Pages (from-to)225-238
Number of pages14
JournalCell Biology and Toxicology
Issue number3
StatePublished - Jun 2010


  • Intestine
  • Microvilli
  • Nanomaterials
  • Titanium dioxide
  • Toxicity

ASJC Scopus subject areas

  • Toxicology
  • Cell Biology
  • Health, Toxicology and Mutagenesis


Dive into the research topics of 'Toxicity and cellular responses of intestinal cells exposed to titanium dioxide'. Together they form a unique fingerprint.

Cite this