Publicado

2018-04-01

Evaluación del efecto genotóxico y mutagénico en linfocitos humanos expuestos a nanotubos de carbono modificados

Evaluation of the genotoxic and mutagenic effect in human lymphocytes exposed to modified carbon nanotubes

Palabras clave:

nanotubos de carbono, genotoxicidad, pruebas de mutagenicidad, linfocitos (es)
carbon nanotubes, genotoxicity, mutagenicity tests, lymphocytes (en)

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Objetivo: evaluar efecto genotóxico y mutagénico en linfocitos humanos expuestos a nanotubos de carbono (NTC) prístinos y dopados con Nitrógeno. Métodos: linfocitos humanos fueron expuestos a NTC dopados y prístinos (0.08, 0.09, 0.1mg/mL), se evaluó alteraciones cromosómicas e intercambio de cromátidas hermanas (ICH). Resultados: se presentaron rupturas cromatídicas y cromosómicas en linfocitos expuestos a 0.1mg/mL y 0.08mg/mL de NTC prístinos. NTC dopados, indujeron cromosomas dicéntricos y anillos cromosómicos. Se presentó diferencia significativa en el porcentaje de ICH de células tratadas con NTC dopados versus control negativo y NTC prístinos (p<0.0001). Conclusión: la concentración más alta de NTC prístinos indujo daños cromatídicos y cromosómicos; aunque el porcentaje de la población con daño fue inferior al 10%, se consideran perjudiciales para las células. Linfocitos tratados con NTC dopados presentaron menores porcentajes de AC y altos valores en ICH, lo que muestra mayor reparación de material genético con estos compuestos.
Objective: evaluate the genotoxic and mutagenic effect in human lymphocytes exposed to pristine and N-doped carbon nanotubes. Methods: Methods: human lymphocytes were exposed to pristine and N-doped carbon nanotubes (NTC) (0.08, 0.09, 0.1mg/mL). Sister chromatid exchange (SCE) and chromosomal alterations (CA) tests were evaluated. Results: chromatid breaks and chromosomal breaks (double strand breaks) were identified in lymphocytes exposed to 0.1 and 0.08 mg/mL of the pristine CNT. N-doped CNT, induced dicentric chromosomes and chromosomal rings. There was significant difference in the percentage of SCE of cells treated with doped NTC versus negative control and pristine NTC (p<0.0001). Conclusion: the highest concentration of pristine CNTs induced the most chromatid and chromosomal damage. Although the percentage was less than 10%, such degree of damage is considered harmful to cells. Lymphocytes treated with N-doped CNT presented lower percentages of CA and high percentage of SCE, which shows a greater repair of genetic material with these compounds.

Citas

Chatterjee, N., Yang, J., Kim, S., Woo, S. and Choi, J., Diameter size and aspect ratio as critical determinants of uptake, stress response, global metabolomics and epigenetic alterations in multi-wall carbon nanotubes. Carbon, 108, pp. 529-540, 2016. DOI: 10.1016/j.carbon.2016.07.031

Van Berlo, D., Clift, M.J., Albrecht, C. and Schins, R.P., Carbon nanotubes: an insight into the mechanisms of their potential genotoxicity. Swiss Med Wkly, 142, pp. 136-198, 2012. DOI: 10.4414/smw.2012.13698

Thurnherr, T., Brandenberger, C., Fischer, K., Diener, L., Manser, P., Maeder-Althaus, X., et al., A comparison of acute and long-term effects of industrial multiwalled carbon nanotubes on human lung and immune cells in vitro. Toxicol Lett [online]. 200(3), 2011. DOI: 10.1016/j.toxlet.2010.11.012. [Date of reference: June 07th of 2017]. Available at: http://www.sciencedirect.com/science/article/pii/S037 8427410017728?via%3Dihub

Al Moustafa, A.E., Mfoumou, E., Roman, D.E., Nerguizian, V., Alazzam, A., Stiharu, I., et al., Impact of single-walled carbon nanotubes on the embryo: a brief review. Int J Nanomedicine, 11, pp. 11, pp. 349-355, 2016. DOI: 10.2147/IJN.S96361

Vales, G., Rubio, L. and Marcos, R., Genotoxic and cell-transformation effects of multi-walled carbon nanotubes (MWCNT) following in vitro sub-chronic exposures. J Hazard Mater [online]. 306, 2016. DOI: 10.1016/j.jhazmat.2015.12.021. [Date of reference: June 07th of 2017]. Available at: http://europepmc.org/abstract/med/26736170

Lijima, S., Helical microtubules of graphitic carbon. Nature, 354, pp. 56-58, 1991. DOI: 10.1038 / 354056a0

Ursini, C.L., Cavallo, D., Fresegna, A.M., Ciervo, A., Maiello, R., Buresti, G., et al., Comparative cyto-genotoxicity assessment of functionalized and pristine multiwalled carbon nanotubes on human lung epithelial cells. Toxicol in Vitro, 26(6), pp. 831-840, 2012. DOI: 10.1016/j.tiv.2012.05.001

Lanone, S., Andujar, P., Kermanizadeh, A. and Boczkowski, J., Determinants of carbon nanotube toxicity, Adv Drug Deliv Rev [online]. 65(15), 2013. DOI: 10.1016/j.toxrep.2016.01.011. [Date of reference: June 07th of 2017]. Available at: http://www.sciencedirect.com/science/article/pii/S0169409X13001737?via%3Dihub

Nagaraju, K., Reddy, R. and Reddy, N., A review on protein functionalized carbon nanotubes. J Appl Biomater Funct Mater [online]. 13(4), 2015. DOI: 10.5301/jabfm.5000231. [Date of

reference: June 07th of 2017]. Available at: http://www.jab-fm.com/article/a-review-on-protein-functionalized-carbon-nanotubes

Vitkina, T.I., Yankova, V.I., Gvozdenko, T.A., Kuznetsov, V.L., Krasnikov, D.V., Nazarenko, A.V., et al., The impact of multi-walled carbon nanotubes with different amount of metallic impurities on immunometabolic parameters in healthy volunteers. Food Chem Toxicol, 87, pp. 138-147, 2016. DOI: 10.1016/j.fct.2015.11.023.

Ghosh, M., Chakraborty, A. and Mukherjee, A., Cytotoxic, genotoxic and the hemolytic effect of titanium dioxide (TiO2) nanoparticles on human erythrocyte and lymphocyte cells in vitro. J Appl Toxicol, 33(10), pp. 1097-1110, 2013. DOI: 10.1002/jat.2863.

Kuzmany H., Kukovecz A., Simon F., Holzweber M., Kramberger C. and Pichler T., Functionalization of carbon nanotubes, Synth. Met., 141(1), pp. 113-122, 2004.

Glerup M., Krstić V., Ewels C., Holzinger M. and Van Lier 6, Doping of Carbon Nanotubes, in: Doped nanomaterials and nanodevices, 2007, pp. 1-66.

Koós A.A., Dillon F., Obraztsova E. A., Crossley A. and Grobert N., Comparison of structural changes in nitrogen and boron-doped multi-walled carbon nanotubes, Carbon N. Y., 48(11), pp. 3033-3041, Sep. 2010.

Wong B.S., Yoong S.L., Jagusiak A., Panczyk T., Ho H.K., Ang W.H. and Pastorin G., Carbon nanotubes for delivery of small molecule drugs., Adv. Drug Deliv. Rev., 65(15), pp. 1964-2015, 2013.

Werengowska-Ciećwierz, K., Wiśniewski, M., Terzyk, A.P., Roszek, K., Czarnecka, J., Bolibok, P., et al., Conscious changes of carbon nanotubes cytotoxicity by manipulation with selected nanofactors. Appl Biochem Biotechnol, 176(3), pp. 730-741, 2015. DOI: 10.1007/s12010-015-1607-1.

Nakanishi, J., Morimoto, Y., Ogura, I., Kobayashi, N., Naya, M., Ema, M., et al., Risk assessment of the carbon nanotube group. Risk Anal [online]. 35(10), 2015. DOI: 10.1111/risa.12394. [Date of reference: June 07th of 2017]. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736668/

Louro, H., Pinhão, M., Santos, J., Tavares, A., Vital, N. and Silva, M.J., Evaluation of the cytotoxic and genotoxic effects of benchmark multi-walled carbon nanotubes in relation to their physicochemical properties. Toxicol Lett, 262, pp.123-134, 2016. DOI: 10.1016/j.toxlet.2016.09.016.

Dong, J. and Ma, Q., Advances in mechanisms and signaling pathways of carbon nanotube toxicity. Nanotoxicology [online]. 9(5), 2015. DOI: 10.3109/17435390.2015.1009187. [Date of reference: June 07th of 2017]. Available at: http://onlinelibrary.wiley.com/doi/10.1111/risa.12394/full

Takagi, A., Hirose, A., Futakuchi, M., Tsuda, H. and Kanno, J., Dose-dependent mesothelioma induction by intraperitoneal administration of multi-wall carbon nanotubes in p53 heterozygous mice. Cancer Sci, 103(8), pp. 1440-1444, 2012. DOI: 10.1111/j.1349-7006.2012.02318.x

Grosse, Y., Loomis, D., Guyton, K.Z., Lauby-Secretan, B., El Ghissassi, F., Bouvard, V., et al., International agency for research on cancer monograph working group. Carcinogenicity of fluoro-edenite, silicon carbide fibres and whiskers, and carbon nanotubes. Lancet Oncol, 15(13), pp. 1427-1428, 2014. DOI: 10.1016/S1470-2045(14)71109-X.

Møller P. and Jacobsen N.R., Weight of evidence analysis for assessing the genotoxic potential of carbon nanotubes. Critical Reviews in Toxicology 47(10), pp 871-888, 2017. DOI: 10.1080/10408444.2017.1367755.

Khalili Fard, J., Jafari, S. and Eghbal, M.A., A review of molecular mechanisms involved in toxicity of nanoparticles. Adv Pharm Bull, 5(4), pp.447-454, 2015. DOI: 10.15171/apb.2015.061.

Hoyos-Palacio, L.M., Efecto de los catalizadores hierro, cobalto, níquel, molibdeno, y mezclas soportadas sobre sílice sol gel, para la síntesis de nanotubos de carbono mediante deposición química de vapor, Tesis de Doctorado en Ingeniería. Universidad Pontificia Bolivariana, Medellín, Colombia 2010, 204 P.

Uhl, M., Christoph, H. and Siegfried, K., Single-cell gel electrophoresis assays with human-derived hepatoma (Hep G2) cells. Mutat Res [online]. 441(2), 1999. [Date of reference: June 07th of 2017]. Available at: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.21.9716&rep=rep1&type=pdf

Yüzbaşıoğlu, D., Ünal, F., Koç, F., Öztemel, S., Aksoy, H., Mamur, S., et al., Genotoxicity assessment of vaccine adjuvant squalene. Food Chem Toxicol, 56, pp. 240-246, 2013. DOI: 10.1016/j.fct.2013.02.034.

Mamur, S., Yüzbaşıoğlu, D., Unal, F. and Aksoy, H., Genotoxicity of food preservative sodium sorbate in human lymphocytes in vitro. Cytotechnology [online]. 64(5), 2012. DOI: 10.1007/s10616-012-9434-5. [Date of reference: June 07th of 2017]. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432536/

Tavares, A.M., Louro, H., Antunes, S., Quarré, S., Simar, S., De Temmerman, P.J., et al., Genotoxicity evaluation of nanosized titanium dioxide, synthetic amorphous silica and multi-walled carbon nanotubes in human lymphocytes. Toxicol In Vitro, 28(1), pp.60-69, 2014. DOI: 10.1016/j.tiv.2013.06.009.

Cruz-Vallejo, V.L., Reparabilidad durante G1 de las lesiones inductoras de intercambios entre cromatidas hermanas producidas por mitomicina C en células de la glándula salival de raton in vivo. México DF: Universidad Nacional Autónoma de México [en línea] 1991. [Fecha de consulta: 7 de junio de 2017]. Disponible en: https://inis.iaea.org/search/search.aspx?orig_q=RN:24063560

Orecchioni, M., Bedognetti, D., Sgarrella, F., Marincola, F., Bianco, A. and Delogu, L., Impact of carbon nanotubes and graphene on immune cells. J Transl Med [online] 12(1), 2014. DOI: 10.1186/1479-5876-12-138. [Date of reference: June 07th of 2017]. Available at: https://translational-medicine.biomedcentral.com/ articles/10.1186/1479-5876-12-138

Zhao, M.L., Li, D.J., Yuan, L., Yue, Y.C., Liu, H. and Sun, X., Differences in cytocompatibility and hemocompatibility between carbon nanotubes and nitrogen-doped carbon nanotubes. Carbon, 49(9), pp. 3125-3133, 2011. DOI: 10.1016/j.carbon.2011.03.037.

Szendi, K. and Varga, C., Lack of genotoxicity of carbon nanotubes in a pilot study. Anticancer Res [online]. 28(1A), 2008. [Fecha de consulta 7 de junio de 2017]. Disponible en: http://ar.iiarjournals.org/content/28/1A/349.long

Shvedova, A.A., Yanamala, N., Kisin, E.R., Tkach, A.V., Murray, A.R., Hubbs, A., Castranova, V., et al., Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons. Am J Physiol Lung Cell Mol Physiol. 306(2), pp. L170-L182, 2014. DOI: 10.1152/ajplung.00167.2013

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