Expression profiling and pathway analysis of iron oxide nanoparticles toxicity on human lung alveolar epithelial cell line using microarray analysis

Year 2020, Volume: 48 Issue: 4, 309 - 318, 06.07.2020

Hasan Türkez , Mehmet Enes Arslan , Erdal Sönmez , Abdulgani Tatar , Fatime Geyikoğlu , Metin Açıkyıldız

https://doi.org/10.15671/hjbc.736803

Cited By: 1

Abstract

Toxicogenomics is a developing area searching for cellular pathways and mechanisms including cancer, immunological diseases, environmental responses, gene-gene interactions and drug toxicity. Nanoparticles (NPs) become important candidates for analyzing in toxicogenomic experiments because of their unusual properties in various biological activities. Therefore, we examined the nanotoxicity of iron oxide (Fe2O3) on gene expression profiling of human alveolar epithelial cells (HPAEpiC) in the study. For this aim, iron oxide nanoparticles were synthesized by zone melting method and characterized via using X-ray crystallography (XRD) and transmission electron microscope (TEM) techniques. Cell viability and cytotoxicity were determined by 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT), neutral red (NR) and lactate dehydrogenase (LDH) release tests. Whole-genome microarray expression analysis was performed to explore the effects of iron oxide nanoparticles on gene expression in cultured human alveolar epithelial cells. For further analyses, these genes were functionally classified by using DAVID (The Database for Annotation, Visualization and Integrated Discovery) with gene ontology (GO) analysis. The results from this study indicated that iron oxide-mediated toxicity directly or indirectly affecting the regulation of cell proliferation, response to hormone stimulus, estrogen stimulus, cytokine activity and blood circulation by stimulating diverse genes.

Keywords

Iron oxide nanoparticles, Microarray analysis, Toxicogenomics, Human alveolar epithelial cells, DAVID analysis

References

• 1. M.R. Gwinn, V. Vallyathan, Nanoparticles: Health effects - Pros and cons, Environ. Health Perspect. 114 (2006) 1818–1825. https://doi.org/10.1289/ehp.8871.
• 2. C. Corot, P. Robert, J.M. Idée, M. Port, Recent advances in iron oxide nanocrystal technology for medical imaging, Adv. Drug Deliv. Rev. 58 (2006) 1471–1504. https://doi.org/10.1016/j.addr.2006.09.013.
• 3. A. Srinivas, P.J. Rao, G. Selvam, A. Goparaju, B.P. Murthy, N.P. Reddy, Oxidative stress and inflammatory responses of rat following acute inhalation exposure to iron oxide nanoparticles, Hum. Exp. Toxicol. 31 (2012) 1113–1131. https://doi.org/10.1177/0960327112446515.
• 4. A. Aston, Beaming in On Nano Gold., BusinessWeek. (2005) 122. http://www.bloomberg.com/news/articles/2005-06-26/nanotech-beaming-in-on-nano-gold.
• 5. M.C. Roco, Environmentally Responsible Development of Nanotechnology, Environ. Sci. Technol. 39 (2005) 106A-112A. https://doi.org/10.1021/es053199u.
• 6. S. Gupta, C.A. Pattillo, S. Wagh, Effect of Remittances on Poverty and Financial Development in Sub-Saharan Africa, World Dev. 37 (2009) 104–115.
• 7. P. Kucheryavy, J. He, V.T. John, P. Maharjan, L. Spinu, G.Z. Goloverda, V.L. Kolesnichenko, Superparamagnetic iron oxide nanoparticles with variable size and an iron oxidation state as prospective imaging agents, Langmuir. 29 (2013) 710–716. https://doi.org/10.1021/la3037007.
• 8. U. Cornell, R.M., Schwertmann, The iron oxides: structure, properties, reactions, occurrence and uses, 2003. https://doi.org/10.1180/minmag.1997.061.408.20.
• 9. M. Babincová, P. Babinec, C. Bergemann, High-gradient magnetic capture of ferrofluids: Implications for drug targeting and tumor embolization, Zeitschrift Fur Naturforsch. - Sect. C J. Biosci. 56 (2001) 909–911.
• 10. B. Bonnemain, Superparamagnetic agents in magnetic resonance imaging: physicochemical characteristics and clinical applications. A review., J. Drug Target. 6 (1998) 167–174. https://doi.org/10.3109/10611869808997890.
• 11. S.J. Bulera, S.M. Eddy, E. Ferguson, T. a Jatkoe, J.F. Reindel, M.R. Bleavins, F. a De La Iglesia, RNA expression in the early characterization of hepatotoxicants in Wistar rats by high-density DNA microarrays., Hepatology. 33 (2001) 1239–58. https://doi.org/10.1053/jhep.2001.23560.
• 12. T.P. Reilly, M. Bourdi, J.N. Brady, C.A. Pise-Masison, M.F. Radonovich, J.W. George, L.R. Pohl, Expression profiling of acetaminophen liver toxicity in mice using microarray technology., Biochem. Biophys. Res. Commun. 282 (2001) 321–8. https://doi.org/10.1006/bbrc.2001.4576.
• 13. J.F. Waring, R. Ciurlionis, R. a. Jolly, M. Heindel, R.G. Ulrich, Microarray analysis of hepatotoxins in vitro reveals a correlation between gene expression profiles and mechanisms of toxicity, Toxicol. Lett. 120 (2001) 359–368. https://doi.org/10.1016/S0378-4274(01)00267-3.
• 14. H. Turkez, F. Geyikoglu, Y.I. Mokhtar, B. Togar, Eicosapentaenoic acid protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced hepatic toxicity in cultured rat hepatocytes, Cytotechnology. Ahrenhoers (2012) 15–25. https://doi.org/10.1007/s10616-011-9386-1.
• 15. H. Turkez, E. Sönmez, A. Di Stefano, Y.I. Mokhtar, Health risk assessments of lithium titanate nanoparticles in rat liver cell model for its safe applications in nanopharmacology and nanomedicine., Cytotechnology. 68 (2016) 291–302. https://doi.org/10.1007/s10616-014-9780-6.
• 16. R.R. Kasar, N.G. Deshpande, Y.G. Gudage, J.C. Vyas, R. Sharma, Studies and correlation among the structural, optical and electrical parameters of spray-deposited tin oxide (SnO2) thin films with different substrate temperatures, Phys. B Condens. Matter. 403 (2008) 3724–3729.
• 17. N. Fernández-Bertólez, C. Costa, M.J. Bessa, M. Park, M. Carriere, F. Dussert, J.P. Teixeira, E. Pásaro, B. Laffon, V. Valdiglesias, Assessment of oxidative damage induced by iron oxide nanoparticles on different nervous system cells, Mutat. Res. Toxicol. Environ. Mutagen. 845 (2019) 402989. https://doi.org/10.1016/j.mrgentox.2018.11.013.
• 18. Ç. Dönmez Güngüneş, Ş. Şeker, A.E. Elçin, Y.M. Elçin, A comparative study on the in vitro cytotoxic responses of two mammalian cell types to fullerenes, carbon nanotubes and iron oxide nanoparticles, Drug Chem. Toxicol. 40 (2017) 215–227. https://doi.org/10.1080/01480545.2016.1199563.
• 19. R. Hardman, A toxicologic review of quantum dots: toxicity depends on physicochemical and environmental factors., Environ. Health Perspect. 114 (2006) 165–72.
• 20. Y. Wang, L. Deng, A. Caballero-Guzman, B. Nowack, Are engineered nano iron oxide particles safe? an environmental risk assessment by probabilistic exposure, effects and risk modeling, Nanotoxicology. 10 (2016) 1545–1554. https://doi.org/10.1080/17435390.2016.1242798.
• 21. D.M. Brown, M.R. Wilson, W. MacNee, V. Stone, K. Donaldson, Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress in the enhanced activity of ultrafines., Toxicol. Appl. Pharmacol. 175 (2001) 191–9. https://doi.org/10.1006/taap.2001.9240.
• 22. N. Lewinski, V. Colvin, R. Drezek, Cytotoxicity of nanoparticles., Small. 4 (2008) 26–49. https://doi.org/10.1002/smll.200700595.
• 23. H. Zou, N.K. Osborn, J.J. Harrington, K.K. Klatt, J.R. Molina, L.J. Burgart, D.A. Ahlquist, Frequent methylation of Eyes absent 4 gene in Barrett’s esophagus and esophageal adenocarcinoma, Cancer Epidemiol. Biomarkers Prev. 14 (2005) 830–834. https://doi.org/10.1158/1055-9965.EPI-04-0506.
• 24. Z. Liu, X. Chen, Y. Wang, H. Peng, Y. Wang, Y. Jing, H. Zhang, PDK4 protein promotes tumorigenesis through activation of cAMP-response element-binding protein (CREB)-Ras homolog enriched in brain (RHEB)-mTORC1 signaling cascade, J. Biol. Chem. 289 (2014) 29739–29749. https://doi.org/10.1074/jbc.M114.584821.
• 25. J. Gu, J. Chen, J. Feng, Y. Liu, Q. Xue, G. Mao, L. Gai, X. Lu, R. Zhang, J. Cheng, Y. Hu, M. Shao, H. Shen, J. Huang, Overexpression of ADAMTS5 can regulate the migration and invasion of non-small cell lung cancer., Tumour Biol. 37 (2016) 8681–9. https://doi.org/10.1007/s13277-015-4573-x.
• 26. N. Singh, G.J.S. Jenkins, R. Asadi, S.H. Doak, Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION), Nano Rev. Exp. 1 (2010). https://doi.org/10.3402/NR.V1I0.5358.
• 27. S. Rajiv, J. Jerobin, V. Saranya, M. Nainawat, A. Sharma, P. Makwana, C. Gayathri, L. Bharath, M. Singh, M. Kumar, A. Mukherjee, N. Chandrasekaran, Comparative cytotoxicity and genotoxicity of cobalt (II, III) oxide, iron (III) oxide, silicon dioxide, and aluminum oxide nanoparticles on human lymphocytes in vitro, Hum. Exp. Toxicol. 35 (2015) 170–183. https://doi.org/10.1177/0960327115579208.
• 28. L. Mirabello, E.R. Macari, L. Jessop, S.R. Ellis, T. Myers, N. Giri, A.M. Taylor, K.E. McGrath, J.M. Humphries, B.J. Ballew, M. Yeager, J.F. Boland, J. He, B.D. Hicks, L. Burdett, B.P. Alter, L. Zon, S.A. Savage, Whole-exome sequencing and functional studies identify RPS29 as a novel gene mutated in multicase Diamond-Blackfan anemia families, Blood. 124 (2014) 24–32. https://doi.org/10.1182/blood-2013-11-540278.
• 29. S.K. Saha, H.Y. Choi, B.W. Kim, A.A. Dayem, G.-M. Yang, K.S. Kim, Y.F. Yin, S.-G. Cho, KRT19 directly interacts with β-catenin/RAC1 complex to regulate NUMB-dependent NOTCH signaling pathway and breast cancer properties., Oncogene. (2016). https://doi.org/10.1038/onc.2016.221.
• 30. X. Hu, P. Zhang, Z. Xu, H. Chen, X. Xie, GPNMB enhances bone regeneration by promoting angiogenesis and osteogenesis: potential role for tissue engineering bone., J. Cell. Biochem. 114 (2013) 2729–37. https://doi.org/10.1002/jcb.24621.
• 31. D. Szklarczyk, A. Franceschini, S. Wyder, K. Forslund, D. Heller, J. Huerta-Cepas, M. Simonovic, A. Roth, A. Santos, K.P. Tsafou, M. Kuhn, P. Bork, L.J. Jensen, C. von Mering, STRING v10: protein-protein interaction networks, integrated over the tree of life., Nucleic Acids Res. 43 (2015) D447-52. https://doi.org/10.1093/nar/gku1003.
• 32. M.S. Fawzy, A.R. Elfayoumi, R.H. Mohamed, I.R.A. Fatah, S.F. Saadawy, Cyclooxygenase 2 (rs2745557) Polymorphism and the Susceptibility to Benign Prostate Hyperplasia and Prostate Cancer in Egyptians, Biochem. Genet. 54 (2016) 326–336. https://doi.org/10.1007/s10528-016-9722-4.
• 33. Y. Dai, Y. Wu, Y. Li, Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinson’s disease susceptibility in Chinese Han population., Int. J. Clin. Exp. Pathol. 8 (2015) 13495–9. http://www.ncbi.nlm.nih.gov/pubmed/26722563%5Cnhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4680508.
• 34. Y. Zhang, H. Su, K. Pan, L. Zhang, J. Ma, L. Shen, J.-Y. Li, W.-D. Liu, I. Oze, K. Matsuo, Y. Yuasa, W. You, Methylation status of blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population., Cancer Epidemiol. Biomarkers Prev. 23 (2014) 2019–26. https://doi.org/10.1158/1055-9965.EPI-13-0994.
• 35. J. Hua, Z.-G. He, D.-H. Qian, S.-P. Lin, J. Gong, H.-B. Meng, T.-S. Yang, W. Sun, B. Xu, B. Zhou, Z.-S. Song, Angiopoietin-1 gene-modified human mesenchymal stem cells promote angiogenesis and reduce acute pancreatitis in rats., Int. J. Clin. Exp. Pathol. 7 (2014) 3580–95. http://www.ncbi.nlm.nih.gov/pubmed/25120736 (accessed January 30, 2017).
• 36. J. Zhao, L. Chen, B. Shu, J. Tang, L. Zhang, J. Xie, X. Liu, Y. Xu, S. Qi, Angiopoietin-1 Protects the Endothelial Cells Against Advanced Glycation End Product Injury by Strengthening Cell Junctions and Inhibiting Cell Apoptosis, J. Cell. Physiol. 230 (2015) 1895–1905. https://doi.org/10.1002/jcp.24920.
• 37. W. Li, Y. You, X. Zhang, Y. Song, H. Xiang, X. Peng, J. Qin, G. Tan, Amplification of chromosome 8q21-qter associated with the acquired paclitaxel resistance of nasopharyngeal carcinoma cells., Int. J. Clin. Exp. Pathol. 8 (2015) 12346–56. http://www.ncbi.nlm.nih.gov/pubmed/26722421 (accessed January 30, 2017).