Toxicity and cellular responses of intestinal cells exposed to titanium dioxide.
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 (TiO(2)), could cross the epithelium layer by employing both toxicity and mechanistic studies. This study provides evidence that at 10 microg/mL and above, TiO(2) nanoparticles cross the epithelial lining of the intestinal model by transcytosis, albeit at low levels. TiO(2) was able to penetrate into and through the cells without disrupting junctional complexes, as measured by gamma-catenin. To monitor the epithelial integrity, transepithelial electrical resistance (TEER) was employed and determined low concentrations (10 or 100 microg/mL) of TiO(2) do not disrupt epithelial integrity. Live/dead analysis results did not show cell death after exposure to TiO(2). In addition, at 10 microg/mL (and above) TiO(2) 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.).
Koeneman
Brian A
BA
Cellular and Molecular Biosciences Faculty, School of Life Sciences, Arizona State University, PO Box 874501, Tempe, AZ 85287-4501, USA.
Zhang
Yang
Y
Westerhoff
Paul
P
Chen
Yongsheng
Y
Crittenden
John C
JC
Capco
David G
DG
D018938:Caco-2 Cells; D017097:Electric Impedance; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods; D051185:gamma Catenin / Q000378:metabolism
D051185:gamma Catenin; C009495:titanium dioxide; D014025:Titanium