Predictive Toxicology of cobalt ferrite nanoparticles: comparative in-vitro study of different cellular models using methods of knowledge discovery from data

Background: Cobalt-ferrite nanoparticles (Co-Fe NPs) are attractive for nanotechnology-based therapies. Thus, exploring their effect on viability of seven different cell lines representing different organs of the human body is highly important. Methods: The toxicological effects of Co-Fe NPs were studied by in-vitro exposure of A549 and NCIH441 cell-lines (lung), precision-cut lung slices from rat, HepG2 cell-line (liver), MDCK cell-line (kidney), Caco-2 TC7 cell-line (intestine), TK6 (lymphoblasts) and primary mouse dendritic-cells. Toxicity was examined following exposure to Co-Fe NPs in the concentration range of 0.05 -1.2 mM for 24 and 72 h, using Alamar blue, MTT and neutral red assays. Changes in oxidative stress were determined by a dichlorodihydrofluorescein diacetate based assay. Data analysis and predictive modeling of the obtained data sets were executed by employing methods of Knowledge Discovery from Data with emphasis on a decision tree model (J48). Results: Different dose–response curves of cell viability were obtained for each of the seven cell lines upon exposure to Co-Fe NPs. Increase of oxidative stress was induced by Co-Fe NPs and found to be dependent on the cell type. A high linear correlation (R2=0.97) was found between the toxicity of Co-Fe NPs and the extent of ROS generation following their exposure to Co-Fe NPs. The algorithm we applied to model the observed toxicity belongs to a type of supervised classifier. The decision tree model yielded the following order with decrease of the ranking parameter: NP concentrations (as the most influencing parameter), cell type (possessing the following hierarchy of cell sensitivity towards viability decrease: TK6 > Lung slices > NCIH441 > Caco-2 = MDCK > A549 > HepG2 = Dendritic) and time of exposure, where the highest-ranking parameter (NP concentration) provides the highest information gain with respect to toxicity. The validity of the chosen decision tree model J48 was established by yielding a higher accuracy than that of the well-known “naive bayes” classifier. Conclusions: The observed correlation between the oxidative stress, caused by the presence of the Co-Fe NPs, with the hierarchy of sensitivity of the different cell types towards toxicity, suggests that oxidative stress is one possible mechanism for the toxicity of Co-Fe NPs. Keywords: Nanotoxicology, Cobalt-ferrite nanoparticles, Comparative cytotoxicity, Data mining

HOREV-AZARIA Limor;  BALDI Giovanni;  BENO Delila;  BONACCHI Daniele;  GOLLA-SCHINDLER Ute;  KIRKPATRICK James C;  KOLLE Susanne;  LANDSIEDEL Robert;  MAIMON Oded;  MARCHE Patrice N;  PONTI Jessica;  ROMANO Roni;  ROSSI Francois;  SOMMER Dieter;  UBOLDI C.;  UNGER Ronald E;  VILLIERS Christian;  KORENSTEIN Rafi; 

2014-01-23

BIOMED CENTRAL LTD

JRC88239

1743-8977,   

http://www.particleandfibretoxicology.com/content/10/1/32,    https://publications.jrc.ec.europa.eu/repository/handle/JRC88239,   

10.1186/1743-8977-10-32,