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Experimental Design and Predictive Computational Modeling for the Toxicity of Nanomaterials on the Human Epidermal Cells
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International Journal of Biometrics and Bioinformatics (IJBB)
Table of Contents
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Volume:  4    Issue:  2
Pages:  13-99
Publication Date:   May 2010
ISSN (Online): 1985-2347
34 - 41
Natarajan Meghanathan - United States of America
Raphael Isokpehi - United States of America
Hari Har Parshad Cohly - United States of America
Published Date   
CSC Journals, Kuala Lumpur, Malaysia
Keywords   Abstract   References   Cited by   Related Articles   Collaborative Colleague
KEYWORDS:   Biometrics, visual cryptography, iris, authentication 
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Nanomaterials are becoming more commonly used in everyday life, where human beings are becoming exposed to such materials. However, the toxicity of the materials being introduced in our environment is not fully studied. We are currently working on a pilot project to develop computation models that can predict the toxicity of nanomaterials on cell types based on empirical data obtained through monoculture experiments and co-culture experiments. Our hypothesis is that computational approach can be utilized to predict the toxicity and model the intercellular interactions in co-culture studies. The uniqueness of this approach is that we propose to employ computational methods to predict the outcome of co-culture experiments and test the validity of the predictions with cellular biology assays results from co-culture experiments. Human skin cell types such as keratinocytes, melanocytes and dendritic cell lines will be used to mimic the cellular elements of the epidermis. Cytoxicity, genotoxicity and lipid peroxidation assays will be used to measure cytoplasmic, DNA, and lipid membrane damage respectively. The expected results are that the computational approach will use the results from monoculture experiments to generate a preliminary model that will predict the outcome of co-culture experiments. The preliminary model will be further trained using the co-culture experiments conducted to validate the predicted results. 
1 A. R. Murray, E. Kisin, S. S. Leonard, S. H. Young, C. Kommineni, V. E. Kagan, V. Castraova and A. A. Shvedova, “Oxidative Stress and Inflammatory Response in Dermal Toxicity of Single-walled Carbon Nanotubes,” Toxicology, 257(3): 161-171, 2009.
2 E. Sabbioni, S. Fortaner, S. Bosisio, M. Farina, R. Del Torchio, J. Edel and M. Fischbach, “Metabolic Fate of Ultratrace Levels of GeCl4 in the Rat and In Vitrio Studies on its Basal Cytotoxicity and Carcniogenic Potential in Balb/3T3 and HaCaT Cell Lines,” Journal of Applied Toxiciology, 30(1): 34 – 41, 2010.
3 L. Xiao, K. Matsubayashi and N. Miwa, “Inhibitory Effect of the Water-soluble Polymer-wrapped Derivative of Fullerene on UVA-induced Melanogenesis via Downregulation of Tyrosinase Expression in Human Melanocytes and Skin Tissues,” Archives of Dermatological Research, 299(5-6): 245-257, 2007.
4 V. Manolova, A. Flace, M. Bauer, K. Schwarz, P. Saudan and M. F. Bachmann, “Nanomaterials Target Distinct Dendritic Cell Populations according to their Size,” European Journal of Immunology, 38(5): 1404-1413, 2008.
5 B. Kiss, T. Biro, G. Czifra, BI Toth, Z. Kertesz, Z. Szikszai, A. Z. Kiss, I. Juhasz, C. C. Zouboulis and J. Hunyadi, “Investigation of Micronized Titanium Dioxide Penetration in Human Skin Xenografts and its Effect on Cellular Functions of Human Skin-derived Cells,” Experimental Dermatology, 17(8): 659-667, 2008
6 S. Bastian, W. Busch, D. Kuhnel, A. Springer, T. Meissner, R. Holke, S. Scholz, M. Iwe, W. Pompe, M. Gelinsky, A. Potthoff, V. Richter, C. Ikonomidou and K. Schirmer, “Toxicity of Tungsten Carbide and Cobalt-doped Tungsten Carbide Nanomaterials in Mammalian Cells In Vitro,” Environmental Health Perspectives, 117(4):530-536, 2009.
7 G. J. Garcia and J. S. Kimbell, “Deposition of Inhaled Nanomaterials in the Rat Nasal Passages: Dose to the Olfactory Region,” Inhalation Toxicology, 21(14):1165-1175, 2009.
8 F. Li, X. Zhou, J. Zhu, J. Ma, X. Huang and S. T. Wong, “High Content Image Analysis for Human H4 Neuroglioma Cells Exposed to CuO Nanomaterials,” BMC Biotechnology, 7(66), 2007.
9 B. Graham-Evans, H. H. P. Cohly, H. Yu and P. B. Tchounwou, “Arsenic-Induced Genotoxic and Cytotoxic Effects in Human Keratinocytes, Melanocytes and Dendritic Cells,” International Journal of Environmental Research and Public Health, 1(2):83 – 89, 2004.
10 C. Huang, Q. Ke, M. Costa and X. Shi, “Molecular Mechanisms of Arsenic Carcinogenesis,” Molecular and Cellular Biochemistry, 255(1-2):57 – 66, 2004.
11 A. Elder, H. Yang, R. Gwiazda, X. Teng, S. Thurston, H. He and G. Oberdorster, “Testing Nanomaterials of Unknown Toxicity: An Example Based on Platinum Nanomaterials of Different Shapes,” Wiley Advanced Materials, 19(20):3124 – 3129, 2007.
12 S. Y. Shaw, E. C. Westly, M. J. Pittet, A.Subramanian, S. L. Schreiber and R. Weissleder, “Perturbational Profiling of Nanomaterial Biologic Activity,” In Proceedings of the National Academy of Sciences of the United States of America, 105(210):7387 – 7392, 2008.
13 F. Laco, M. Kun, H. J. Weber, S. Ramakrishna and C. K. Chan, “The Dose Effect of Human Bone Marrow-derived Mesenchymal Stem Cells on Epidermal Development in Organotypic Co-culture,” Journal of Dermatological Science, 55(3):150-160, 2009.
14 H. Inano, M. Onoda, N. Inafuku, M. Kubota, Y. Kamada, T. Osawa, H. Kobayashi and K. Wakabayashi, “Chemoprevention by Curcumin during the Promotion State of Tumorigenesis of Mammary Gland in Rats Irradiated with Gamma-rays,” Carcinogenesis, 20(6): 1011-1018, 1999.
15 J. A. Buege and S. D. Aust, “Microsomal Lipid Peroxidation,” Methods in Enzymology, 52: 302-310, 1978.
1 Jackson State University (JSU)
2 Jackson State University
3 Jackson State University
4 University of Toronto
Natarajan Meghanathan : Colleagues
Raphael Isokpehi : Colleagues
Hari Har Parshad Cohly : Colleagues  
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