Journal Article

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

Beno, Delila, Uboldi, Chiara, Rossi, François, Kolle, Susanne, Golla-Schindler, Ute, Romano, Roni, Korenstein, Rafi, Baldi, Giovanni, Unger, Ronald E, Kirkpatrick, James C, Horev-Azaria, Limor, Sommer, Dieter, Landsiedel, Robert, Maimon, Oded, Ponti, Jessica, Villiers, Christian, Bonacchi, Daniel, Marche, Patrice N

2013

Overview

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 (R 2 =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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BioMed Central (Springer Nature)
• Subject: Algorithms / Animals / Artificial Intelligence / Biomedical and Life Sciences / Biomedicine / Biotechnology industry / Caco-2 Cells / Cell Survival - drug effects / Cobalt / Cobalt - toxicity / Cytotoxicity / Data Mining / Decision Support Techniques / Decision Trees / Dogs / Dose-Response Relationship, Drug / Environmental Health / Exposure / Ferric Compounds - toxicity / Ferrites (Magnetic materials) / Health aspects / Hep G2 Cells / Humans / Information management / Life Sciences / Linear Models / Liver / Madin Darby Canine Kidney Cells / Metal Nanoparticles / Methods / Mice / Nanoparticles / Nanotechnology / Oxidative stress / Oxidative Stress - drug effects / Pharmacology/Toxicology / Pneumology/Respiratory System / Primary Cell Culture / Public Health / Rankings / Rats / Reactive Oxygen Species - metabolism / Santé publique et épidémiologie / Studies / Time Factors / Tissue Culture Techniques / Toxicity / Toxicology / Toxicology - methods