TY - JOUR
T1 - Toxicity and cellular responses of intestinal cells exposed to titanium dioxide
AU - Koeneman, Brian A.
AU - Zhang, Yang
AU - Westerhoff, Paul
AU - Chen, Yongsheng
AU - Crittenden, John C.
AU - Capco, David
N1 - Funding Information:
Although the research described in this article has been funded wholly or in part by the United States Environmental Protection Agency through grant/cooperative agreement RD831713 to Arizona State University, it has not been subjected to the Agency's required peer and policy review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred.
PY - 2010/6
Y1 - 2010/6
N2 - 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.).
AB - 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.).
KW - Intestine
KW - Microvilli
KW - Nanomaterials
KW - Titanium dioxide
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=77952093646&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952093646&partnerID=8YFLogxK
U2 - 10.1007/s10565-009-9132-z
DO - 10.1007/s10565-009-9132-z
M3 - Article
C2 - 19618281
AN - SCOPUS:77952093646
SN - 0742-2091
VL - 26
SP - 225
EP - 238
JO - Cell Biology and Toxicology
JF - Cell Biology and Toxicology
IS - 3
ER -