Abstract
The gastrointestinal uptake of different crystal structures of TiO2 was investigated using Caco-2 intestinal cells. Caco-2 monolayers exhibited time-dependent, saturable uptake of Ti from TiO2 exposures of 1 mgl(-1) over 24h, which was influenced by crystal type. Initial uptake rates were 5.3, 3.73, 3.58 and 4.48 nmol mg(-1)protein h(-1) for bulk, P25, anatase and rutile forms respectively. All exposures caused elevations of Ti in the cells relative to the control (ANOVA P<0.05). Electron micrographs of the Caco-2 monolayer showed the presence of particles inside the cells, and energy dispersive spectroscopy (EDS) confirmed the composition as TiO2. Incubating the cells with 120 IU nystatin (putative endocytosis inhibitor) or 100 μmol l(-1) vanadate (ATPase inhibitor) caused large increases in Ti accumulation for all crystal types relative to controls (ANOVA P<0.05), except for the rutile form with vanadate. Incubating the cells with 90 μmol l(-1) genistein (tyrosine kinase inhibitor) or 27 μmol l(-1) chloropromazine (clathrin-mediated endocytosis inhibitor) caused a large decrease in Ti accumulation relative to the controls (ANOVA P<0.05). Cell viability measures were generally good (low LDH leak, normal cell morphology), but there were some changes in the electrolyte composition (K(+), Na(+), Ca(2+), Mg(2+)) of exposed cells relative to controls. A rise in total Ca(2+) concentration in the cells was observed for all TiO2 crystal type exposures. Overall, the data shows that Ti accumulation for TiO2 NP exposure in Caco-2 cells is crystal structure-dependent, and that the mechanism(s) involves endocytosis of intact particles.
DOI
10.1016/j.toxlet.2014.02.014
Publication Date
2014-05-02
Publication Title
Toxicol Lett
Volume
226
Issue
3
Organisational Unit
School of Biological and Marine Sciences
Keywords
Caco-2, Electrolyte homeostasis, Endocytosis, Titanium dioxide nanoparticles, Uptake mechanism, Amiloride, Caco-2 Cells, Cell Survival, Chlorpromazine, Crystallization, Genistein, Humans, Intestinal Mucosa, Intestines, Nanoparticles, Nystatin, Particle Size, Titanium, Vanadates
First Page
264
Last Page
276
Recommended Citation
Gitrowski, C., Al-Jubory, A., & Handy, R. (2014) 'Uptake of different crystal structures of TiO₂ nanoparticles by Caco-2 intestinal cells.', Toxicol Lett, 226(3), pp. 264-276. Available at: https://doi.org/10.1016/j.toxlet.2014.02.014
