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Surface properties of pulmonary surfactant in the presence of metal oxide nanoparticles
Abstracts / Toxicology Letters 258S (2016) S62–S324
P17-030 Classification nano-SAR modeling of metal oxides nanoparticles genotoxicity based on comet assay data A. Golbamaki 1,∗ , N. Golbamaki 2 , N. Sizochenko 3 , B. Rasulev 5 , A. Cassano 6 , T. Puzyn 4 , J. Leszczynski 3 , E. Benfenati 1 1
Laboratory of Environmental Chemistry and Toxicology at the Mario Negri Institute, Milan, Italy 2 INERIS, DRC/VIVA/METO, Parc ALATA, BP 2, 60550 Verneuil en Halatte, France 3 Interdisciplinary Center for Nanotoxicity, Jackson State University, Jackson, MS USA 4 Laboratory of Environmental Chemometrics, Faculty of Chemistry, University of Gdansk, Gdansk, Poland 5 Center for Computationally Assisted Science and Technology, North Dakota State University, Fargo, ND, USA 6 Liverpool John Moores University, Liverpool, UK In nearly a decade of vigorous attempt in the toxicology and exposure research carried out to provide evidence for the assessment of health and environmental risks of nanomaterials (NMs), some progress has been made in generating the health effects and exposure data needed to perform risk assessment and develop risk management guidance. Quantitative Structure Activity Relationship ((Q)SAR) models are a powerful tool for rapid screening of large numbers and types of materials with advantage of saving time, funds and animal suffering. In this work we present first (Q)SAR models developed to predict genotoxicity of metal oxide NMs by using large initial sets of nano descriptors. We used a dataset containing in vitro comet assay genotoxicity for 16 nano metal oxides with different chemical core composition. This multi-source data was retrieved from genotoxicity profiles collected in our previous work. To properly analyse the data, we used a weight of evidence approach for evaluation of quality of the comet in vitro data for (Q)SAR modelling. Subsequently, based on the quality of checked dataset, we assigned genotoxic or non-genotoxic property to each metal core composition. By employing orthogonal partial least squares–discriminant analysis (OPLS-DA) method, nano-(Q)SAR models were derived with significant predictive power: accuracy 0.83 and 1. Conventional molecular descriptors and quantum chemical descriptors together with descriptors based on metalligand binding properties have been analysed to discuss the key factors affecting genotoxicity of metal oxide NMs. All derived models involve descriptors that describe possible structural factors influencing genotoxic behaviour of metal oxide NMs. http://dx.doi.org/10.1016/j.toxlet.2016.06.1950 P17-031 Surface properties of pulmonary surfactant in the presence of metal oxide nanoparticles D. Kondej 1,∗ , T.R. Sosnowski 2 1 Department of Chemical, Aerosol and Biological Hazards, Central Institute for Labour Protection – National Research Institute, Warsaw, Poland 2 Faculty of Chemical and Process Engineering, Warsaw University of Technology, Warsaw, Poland
This study was aimed to evaluate the influence of metal oxide nanoparticles (MON) on the surface properties of the pulmonary surfactant (PS), which constitutes the first barrier separating the lung tissue from inhaled air.
S271
Changes in surface pressure over time in the presence of aluminum oxide, zinc oxide and cerium oxide nanoparticles (Sigma-Aldrich) were tested using DeltaPi microtensiometer (Kibron Inc., Finland). The animal-derived surfactant preparation (Beractantum; Abbott Laboratories, France) was used as model PS. The tests were carried out at different MON concentrations (ranging up to 1 mg/ml) with the constant concentration of PS solution (1.25 mg phospholipids/ml). It was found that MON caused an increase in surface pressure at the liquid–air interface. The intensity of these changes depends on the chemical structure, size distribution, specific surface area and concentration of MON in the liquid phase. The largest increase in surface pressure (8.0 ± 1.3 mN/m) was observed after 600 s in the presence of aluminum oxide nanoparticles, which were characterized by the smallest dimensions (13 nm; TEM) and the largest surface area (139.8 m2 /g; BET). Results show that MON may influence the PS surface activity in vivo and cause a disturbance of biochemical processes in the respiratory system. This paper was prepared on the basis of the results of the task No. 2.Z.07 carried out within the National Programme “Improvement of safety and working conditions” partly supported in 20142016 within the scope of state services – by the Ministry of Labour and Social Policy. CIOP-PIB was the Programme’s main co-ordinator. http://dx.doi.org/10.1016/j.toxlet.2016.06.1951 P17-032 Genotoxicity analysis of nano and micro particles of hydroxyapatite in human mesenchymal stem cells S. Batistuzzo 1,∗ , J.F. De Queiroz 1 , G. Chaves Filho 1 , S.M. Moreira 1 , M.R. Fernandes 2 1
Laboratório de Biologia Molecular e Genômica, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil 2 Faculdade de Medicina Dentária, Universidade do Porto, Porto, Portugal Nano and micro hydroxyapatite (HA) particles are being largely developed for various biomedical applications like as hard tissue replacement. These materials can influence the cell behavior regarding viability and differentiation. Therefore, assays to evaluate biocompatibility, including genotoxic studies, should be performed. The aim of this study is to investigate the risk/benefit ratio of micro and nano HA particles for bone regenerative medicine. For this purpose, human mesenchymal stem cells (hMSC) were isolated from umbilical cord, characterized and exposed to commercially available nano (nanoXIM·HAp102® ; Fluidinova, S. A.) and micro (Plasma Biotal) HA particles (0.1, 1 and 10 g/mL) for 24 h. Cell behavior was analyzed 1, 3 and 7 days after the exposure to the particles. Cultures performed in the absence of particles were used as control. Both kind of HA particles do not affect hMSC viability (p < 0.05). However, compared to control, higher concentrations seem to induce an early osteogenic differentiation, in the absence of any osteogenic inductor. This was evidenced by anticipated peak levels of alkaline phosphatase activity (p < 0.05) and matrix mineralization (p < 0.01). No alteration was observed at oxidative state and genetic stability, performed with measurement of antioxidant enzymes (Superoxide dismutase and Catalase) and CBMN (Cytokinesis-block micronucleus) assay. Our findings suggest that HA exposure does not have genotoxic effect during osteogenic dif-
P17-030 Classification nano-SAR modeling of metal oxides nanoparticles genotoxicity based on comet assay data A. Golbamaki 1,∗ , N. Golbamaki 2 , N. Sizochenko 3 , B. Rasulev 5 , A. Cassano 6 , T. Puzyn 4 , J. Leszczynski 3 , E. Benfenati 1 1
Laboratory of Environmental Chemistry and Toxicology at the Mario Negri Institute, Milan, Italy 2 INERIS, DRC/VIVA/METO, Parc ALATA, BP 2, 60550 Verneuil en Halatte, France 3 Interdisciplinary Center for Nanotoxicity, Jackson State University, Jackson, MS USA 4 Laboratory of Environmental Chemometrics, Faculty of Chemistry, University of Gdansk, Gdansk, Poland 5 Center for Computationally Assisted Science and Technology, North Dakota State University, Fargo, ND, USA 6 Liverpool John Moores University, Liverpool, UK In nearly a decade of vigorous attempt in the toxicology and exposure research carried out to provide evidence for the assessment of health and environmental risks of nanomaterials (NMs), some progress has been made in generating the health effects and exposure data needed to perform risk assessment and develop risk management guidance. Quantitative Structure Activity Relationship ((Q)SAR) models are a powerful tool for rapid screening of large numbers and types of materials with advantage of saving time, funds and animal suffering. In this work we present first (Q)SAR models developed to predict genotoxicity of metal oxide NMs by using large initial sets of nano descriptors. We used a dataset containing in vitro comet assay genotoxicity for 16 nano metal oxides with different chemical core composition. This multi-source data was retrieved from genotoxicity profiles collected in our previous work. To properly analyse the data, we used a weight of evidence approach for evaluation of quality of the comet in vitro data for (Q)SAR modelling. Subsequently, based on the quality of checked dataset, we assigned genotoxic or non-genotoxic property to each metal core composition. By employing orthogonal partial least squares–discriminant analysis (OPLS-DA) method, nano-(Q)SAR models were derived with significant predictive power: accuracy 0.83 and 1. Conventional molecular descriptors and quantum chemical descriptors together with descriptors based on metalligand binding properties have been analysed to discuss the key factors affecting genotoxicity of metal oxide NMs. All derived models involve descriptors that describe possible structural factors influencing genotoxic behaviour of metal oxide NMs. http://dx.doi.org/10.1016/j.toxlet.2016.06.1950 P17-031 Surface properties of pulmonary surfactant in the presence of metal oxide nanoparticles D. Kondej 1,∗ , T.R. Sosnowski 2 1 Department of Chemical, Aerosol and Biological Hazards, Central Institute for Labour Protection – National Research Institute, Warsaw, Poland 2 Faculty of Chemical and Process Engineering, Warsaw University of Technology, Warsaw, Poland
This study was aimed to evaluate the influence of metal oxide nanoparticles (MON) on the surface properties of the pulmonary surfactant (PS), which constitutes the first barrier separating the lung tissue from inhaled air.
S271
Changes in surface pressure over time in the presence of aluminum oxide, zinc oxide and cerium oxide nanoparticles (Sigma-Aldrich) were tested using DeltaPi microtensiometer (Kibron Inc., Finland). The animal-derived surfactant preparation (Beractantum; Abbott Laboratories, France) was used as model PS. The tests were carried out at different MON concentrations (ranging up to 1 mg/ml) with the constant concentration of PS solution (1.25 mg phospholipids/ml). It was found that MON caused an increase in surface pressure at the liquid–air interface. The intensity of these changes depends on the chemical structure, size distribution, specific surface area and concentration of MON in the liquid phase. The largest increase in surface pressure (8.0 ± 1.3 mN/m) was observed after 600 s in the presence of aluminum oxide nanoparticles, which were characterized by the smallest dimensions (13 nm; TEM) and the largest surface area (139.8 m2 /g; BET). Results show that MON may influence the PS surface activity in vivo and cause a disturbance of biochemical processes in the respiratory system. This paper was prepared on the basis of the results of the task No. 2.Z.07 carried out within the National Programme “Improvement of safety and working conditions” partly supported in 20142016 within the scope of state services – by the Ministry of Labour and Social Policy. CIOP-PIB was the Programme’s main co-ordinator. http://dx.doi.org/10.1016/j.toxlet.2016.06.1951 P17-032 Genotoxicity analysis of nano and micro particles of hydroxyapatite in human mesenchymal stem cells S. Batistuzzo 1,∗ , J.F. De Queiroz 1 , G. Chaves Filho 1 , S.M. Moreira 1 , M.R. Fernandes 2 1
Laboratório de Biologia Molecular e Genômica, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil 2 Faculdade de Medicina Dentária, Universidade do Porto, Porto, Portugal Nano and micro hydroxyapatite (HA) particles are being largely developed for various biomedical applications like as hard tissue replacement. These materials can influence the cell behavior regarding viability and differentiation. Therefore, assays to evaluate biocompatibility, including genotoxic studies, should be performed. The aim of this study is to investigate the risk/benefit ratio of micro and nano HA particles for bone regenerative medicine. For this purpose, human mesenchymal stem cells (hMSC) were isolated from umbilical cord, characterized and exposed to commercially available nano (nanoXIM·HAp102® ; Fluidinova, S. A.) and micro (Plasma Biotal) HA particles (0.1, 1 and 10 g/mL) for 24 h. Cell behavior was analyzed 1, 3 and 7 days after the exposure to the particles. Cultures performed in the absence of particles were used as control. Both kind of HA particles do not affect hMSC viability (p < 0.05). However, compared to control, higher concentrations seem to induce an early osteogenic differentiation, in the absence of any osteogenic inductor. This was evidenced by anticipated peak levels of alkaline phosphatase activity (p < 0.05) and matrix mineralization (p < 0.01). No alteration was observed at oxidative state and genetic stability, performed with measurement of antioxidant enzymes (Superoxide dismutase and Catalase) and CBMN (Cytokinesis-block micronucleus) assay. Our findings suggest that HA exposure does not have genotoxic effect during osteogenic dif-