TY - JOUR
T1 - ZnO nanoparticle tracking from uptake to genotoxic damage in human colon carcinoma cells
AU - Condello, Maria
AU - De Berardis, Barbara
AU - Ammendolia, Maria Grazia
AU - Barone, Flavia
AU - Condello, Giancarlo
AU - Degan, Paolo
AU - Meschini, Stefania
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Zinc Oxide (ZnO) nanoparticles are widely used both in the industry and in biomedical applications for their chemical and physical nanomaterial properties. It is therefore essential to go in depth into the cytotoxicity mechanisms and interactions between nanomaterials and cells. The aim of this work was to evaluate the dissolution of ZnO nanoparticles and their uptake, from a few minutes after treatments up to 24 h. ZnO nanoparticles routes of entry into the human colon carcinoma cells (LoVo) were followed at different times by a thorough ultrastructural investigation and semiquantitative analysis. The intracellular release of Zn2 + ions by Zinquin fluorescent dye, and phosphorylated histone H2AX (γ-H2AX) expression were evaluated. The genotoxic potential of ZnO nanoparticles was also investigated by determining the levels of 8-hydroxyl-2′-deoxyguanosine (8-oxodG). The experimental data show that ZnO nanoparticles entered LoVo cells by either passive diffusion or endocytosis or both, depending on the agglomeration state of the nanomaterial. ZnO nanoparticles coming into contact with acid pH of lysosomes altered organelles structure, resulting in the release of Zn2 + ions. The simultaneous presence of ZnO nanoparticles and Zn2 + ions in the LoVo cells determined the formation of reactive oxygen species at the mitochondrial and nuclear level, inducing severe DNA damage.
AB - Zinc Oxide (ZnO) nanoparticles are widely used both in the industry and in biomedical applications for their chemical and physical nanomaterial properties. It is therefore essential to go in depth into the cytotoxicity mechanisms and interactions between nanomaterials and cells. The aim of this work was to evaluate the dissolution of ZnO nanoparticles and their uptake, from a few minutes after treatments up to 24 h. ZnO nanoparticles routes of entry into the human colon carcinoma cells (LoVo) were followed at different times by a thorough ultrastructural investigation and semiquantitative analysis. The intracellular release of Zn2 + ions by Zinquin fluorescent dye, and phosphorylated histone H2AX (γ-H2AX) expression were evaluated. The genotoxic potential of ZnO nanoparticles was also investigated by determining the levels of 8-hydroxyl-2′-deoxyguanosine (8-oxodG). The experimental data show that ZnO nanoparticles entered LoVo cells by either passive diffusion or endocytosis or both, depending on the agglomeration state of the nanomaterial. ZnO nanoparticles coming into contact with acid pH of lysosomes altered organelles structure, resulting in the release of Zn2 + ions. The simultaneous presence of ZnO nanoparticles and Zn2 + ions in the LoVo cells determined the formation of reactive oxygen species at the mitochondrial and nuclear level, inducing severe DNA damage.
KW - Genotoxicity
KW - Human colon carcinoma cells
KW - Nanoparticles uptake
KW - Oxidative stress
KW - ZnO nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=84975807236&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84975807236&partnerID=8YFLogxK
U2 - 10.1016/j.tiv.2016.06.005
DO - 10.1016/j.tiv.2016.06.005
M3 - Article
AN - SCOPUS:84975807236
VL - 35
SP - 169
EP - 179
JO - Toxicology in Vitro
JF - Toxicology in Vitro
SN - 0887-2333
ER -