Toxicology International (Formerly Indian Journal of Toxicology)

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Mouse Mesothelium-Derived Cell Lines:Models to Assess Cytotoxic Effects of Novel Nanomaterials in vitro and to Ultimately Investigating Carcinogenesis in vivo


Affiliations
1 Department of Medicine, University of Fribourg, Route Albert-Gockel 1, 1700 Fribourg, Switzerland
2 BioNanomaterials Group, AdolpheMerkle Institute, University of Fribourg, Chemin des Verdiers 4, 1700 Fribourg, Switzerland
     

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Novel nanomaterials are continuously produced, but still little is known about their potential toxic and carcinogenic effects. In contrast, crocidolite is one of the best-characterized asbestos types known to induce nanotoxicity and to transform mesothelial cells resulting in malignant mesothelioma. Only in few reports mesothelial or mesothelioma-derived cells were used to investigate nanotoxicity and/or carcinogenicity. Even less studies were carried out with mouse-derived cell lines allowing to investigating nanotoxicity in vivo. Immortalized mesothelial cells from wildtype (iMeso-WT1), from NF2+/- heterozygous (iMeso-NF3) mice and the NF2+/- mouse-derived mesothelioma cell line RN5 were used to compare acute cytotoxicity between novel silica-based manufactured nanoparticles (MNP) and crocidolite. All cell lines were sensitive to crocidolite-induced cytotoxicity, but rather resistant to the spherical MNP, with iMeso-NF3 being the most sensitive and RN5 being the least sensitive cells. Chronic exposure (1 month) of iMeso-NF3 cells to a sub-lethal dose of crocidolite resulted in increased acute resistance to crocidolite. Yet, asbestos-resistant iMeso-NF3 cells didn't induce tumors after intraperitoneal injection, while RN5 cell injection resulted in macroscopic tumors after 5 weeks. Thus, mouse mesothelium-derived cell lines appear well suited to study potential hazardous health effects of MNP.

Keywords

In Vitro Mesothelium Model, NF2, Mesothelial Cells, Asbestos, RN5, Silica Particles.
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  • Altomare, D.A., 2005. A Mouse Model Recapitulating Molecular Features of Human Mesothelioma. Cancer Research 65, 8090–8095. doi:10.1158/0008-5472.CAN-05-2312

  • Blum, W., Pecze, L., Felley-Bosco, E., Schwaller, B., 2015a. Overexpression or absence of calretinin in mouse primary mesothelial cells inversely affects proliferation and cell migration. Respiratory Research 1–16. doi:10.1186/s12931015-0311-6

  • Blum, W., Pecze, L., Felley-Bosco, E., Worthmüller-Rodriguez, J., Wu, L., Vrugt, B., de Perrot, M., Schwaller, B., 2015b. Establishment of immortalized murine mesothelial cells and a novel mesothelioma cell line. In Vitro Cell DevBiol Anim. doi:10.1007/s11626-015-9885-z

  • Blum, W., Schwaller, B., 2013.Calretinin is essential for mesothelioma cell growth/survival in vitro: A potential new target for malignant mesothelioma therapy? Int. J. Cancer 133, 2077–2088. doi:10.1002/ijc.28218

  • Bocchetta, M., Di Resta, I., Powers, A., Fresco, R., Tosolini, A., Testa, J.R., Pass, H.I., Rizzo, P., Carbone, M., 2000. Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity. Proc. Natl. Acad. Sci. U.S.A. 97, 10214–10219.

  • Comertpay, S., Pastorino, S., Tanji, M., Mezzapelle, R., Strianese, O., Napolitano, A., Baumann, F., Weigel, T., Friedberg, J., Sugarbaker, P., Krausz, T., Wang, E., Powers, A., Gaudino, G., Kanodia, S., Pass, H.I., Parsons, B.L., Yang, H., Carbone, M., 2014. Evaluation of clonal origin of malignant mesothelioma. J Transl Med 12, 301–301. doi:10.1186/s12967-014-0301-3

  • Dechezelles, J.-F., Griffete, N., Dietsch, H., Scheffold, F., 2013. A General Method to Label Metal Oxide Particles with Fluorescent Dyes Using Aryldiazonium Salts. Part. Part. Syst. Charact. 30, 579–583.doi:10.1002/ppsc.201300014

  • Donaldson, K., Poland, C.A., 2012. Inhaled nanoparticles and lung cancer - what we can learn from conventional particle toxicology. Swiss Med Wkly. doi:10.4414/smw.2012.13547

  • Donaldson, K., Poland, C.A., 2009. Nanotoxicology: new insights into nanotubes. Nat Nanotechnol 4, 708–710. doi:10.1038/nnano.2009.327

  • Felley-Bosco, E., Stahel, R., 2014. Hippo/YAP pathway for targeted therapy. Transl Lung Cancer Res 3, 75–83. doi:10.3978/j.issn.2218-6751.2014.02.03

  • Graf, C., Gao, Q., Schütz, I., Noufele, C.N., Ruan, W., Posselt, U., Korotianskiy, E., Nordmeyer, D., Rancan, F., Hadam, S., Vogt, A., Lademann, J., Haucke, V., Rühl, E., 2012. Surface functionalization of silica nanoparticles supports colloidal stability in physiological media and facilitates internalization in cells. Langmuir 28, 7598–7613. doi:10.1021/la204913t

  • Henzi, T., Blum, W.-V., Pfefferli, M., Kawecki, T.J., Salicio, V., Schwaller, B., 2009. SV40-Induced Expression of Calretinin Protects Mesothelial Cells from Asbestos Cytotoxicity and May Be a Key Factor Contributing to Mesothelioma Pathogenesis. The American Journal of Pathology 174, 2324–2336. doi:10.2353/ajpath.2009.080352

  • Hillegass, J.M., Shukla, A., Lathrop, S.A., MacPherson, M.B., Beuschel, S.L., Butnor, K.J., Testa, J.R., Pass, H.I., Carbone, M., Steele, C., Mossman, B.T., 2010. Inflammation precedes the development of human malignant mesotheliomas in a SCID mouse xenograft model. Annals of the New York Academy of Sciences 1203, 7–14. doi:10.1111/j.1749-6632.2010.05554.x

  • Horvath, L., Magrez, A., Burghard, M., Kern, K., Forró, L., Schwaller, B., 2013. Evaluation of the toxicity of graphene derivatives on cells of the lung luminal surface. Carbon 64, 45–60. doi:10.1016/j.carbon.2013.07.005

  • Horvath, L., Magrez, A., Golberg, D., Zhi, C., Bando, Y., Smajda, R., Horváth, E., Forró, L., Schwaller, B., 2011. In VitroInvestigation of the Cellular Toxicity of Boron Nitride Nanotubes. ACS Nano 5, 3800–3810. doi:10.1021/nn200139h

  • Jongsma, J., van Montfort, E., Vooijs, M., Zevenhoven, J., Krimpenfort, P., van der Valk, M., van de Vijver, M., Berns, A., 2008. A Conditional Mouse Model for Malignant Mesothelioma. Cancer Cell 13, 261–271. doi:10.1016/j.ccr.2008.01.030

  • Magrez, A., Horváth, L., Smajda, R., Salicio, V., Pasquier, N., Forró, L., Schwaller, B., 2009. Cellular Toxicity of TiO 2-Based Nanofilaments. ACS Nano 3, 2274–2280. doi:10.1021/nn9002067

  • Mosmann, T., 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55–63.

  • Murphy, F.A., Poland, C.A., Duffin, R., Donaldson, K., 2013.Length-dependent pleural inflammation and parietal pleural responses after deposition of carbon nanotubes in the pulmonary airspaces of mice.Nanotoxicology 7, 1157–1167. doi:10.3109/17435390.2012.713527

  • Mutsaers, S.E., 2004. The mesothelial cell. The International Journal of Biochemistry & Cell Biology 36, 9–16. doi:10.1016/S1357-2725(03)00242-5

  • Napolitano, A., Pellegrini, L., Dey, A., Larson, D., Tanji, M., Flores, E.G., Kendrick, B., Lapid, D., Powers, A., Kanodia, S., Pastorino, S., Pass, H.I., Dixit, V., Yang, H., Carbone, M., 2015. Minimal asbestos exposure in germline 1–7. doi:10.1038/onc.2015.243

  • Nymark, P., Jensen, K.A., Suhonen, S., Kembouche, Y., Vippola, M., Kleinjans, J., Catalan, J., Norppa, H., van Delft, J., Briede, J.J., 2014. Free radical scavenging and formation by multi-walled carbon nanotubes in cell free conditions and in human bronchial epithelial cells. Part FibreToxicol 11, –4. doi:10.1186/1743-8977-11-4

  • Pecze, L., Schwaller, B., 2015. Characterization and modeling of Ca(2+) oscillations in mouse primary mesothelial cells. Biochim. Biophys. Acta 1854, 632–645. doi:10.1016/j.bbamcr.2014.12.025

  • Poland, C.A., Miller, M.R., Duffin, R., Cassee, F., 2014. The elephant in the room: reproducibility in toxicology. Part FibreToxicol 11, 42.doi:10.1186/s12989-014-0042-8

  • Robinson, B.W.S., Lake, R.A., 2005. Advances in malignant mesothelioma. N. Engl. J. Med. 353, 1591–1603. doi:10.1056/NEJMra050152

  • Stahel, R.A., Felley-Bosco, E., Opitz, I., Weder, W., 2009. Malignant pleural mesothelioma.Future Oncology 5, 391–402.doi:10.2217/fon.09.7

  • Stark, W.J., Stoessel, P.R., Wohlleben, W., Hafner, A., 2015. ChemSoc Rev. ChemSoc Rev 1–13. doi:10.1039/C4CS00362D

  • Szabolcsi, V., Celio, M.R., 2015. De novo expression of parvalbumin in ependymal cells in response to brain injury promotes ependymal remodeling and wound repair. Glia 63, 567–594. doi:10.1002/glia.22768

  • Thurneysen, C., Opitz, I., Kurtz, S., Weder, W., Stahel, R.A., Felley-Bosco, E., 2009. Functional inactivation of NF2/merlin in human mesothelioma. Lung Cancer 64, 140–147. doi:10.1016/j.lungcan.2008.08.014

  • Verhaegh, N., Blaaderen, A., 1994. Dispersions of rhodamine-labeled silica spheres: synthesis, characterization, and fluorescence confocal scanning laser microscopy. Langmuir.


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  • Mouse Mesothelium-Derived Cell Lines:Models to Assess Cytotoxic Effects of Novel Nanomaterials in vitro and to Ultimately Investigating Carcinogenesis in vivo

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Authors

Sarah Lutz
Department of Medicine, University of Fribourg, Route Albert-Gockel 1, 1700 Fribourg, Switzerland
Perret-Gentil Saskia
Department of Medicine, University of Fribourg, Route Albert-Gockel 1, 1700 Fribourg, Switzerland
Laszlo Pecze
Department of Medicine, University of Fribourg, Route Albert-Gockel 1, 1700 Fribourg, Switzerland
Thomas Henzi
Department of Medicine, University of Fribourg, Route Albert-Gockel 1, 1700 Fribourg, Switzerland
Jean-Francois Dechezelles
BioNanomaterials Group, AdolpheMerkle Institute, University of Fribourg, Chemin des Verdiers 4, 1700 Fribourg, Switzerland
Beat Schwaller
Department of Medicine, University of Fribourg, Route Albert-Gockel 1, 1700 Fribourg, Switzerland
Walter Blum
Department of Medicine, University of Fribourg, Route Albert-Gockel 1, 1700 Fribourg, Switzerland

Abstract


Novel nanomaterials are continuously produced, but still little is known about their potential toxic and carcinogenic effects. In contrast, crocidolite is one of the best-characterized asbestos types known to induce nanotoxicity and to transform mesothelial cells resulting in malignant mesothelioma. Only in few reports mesothelial or mesothelioma-derived cells were used to investigate nanotoxicity and/or carcinogenicity. Even less studies were carried out with mouse-derived cell lines allowing to investigating nanotoxicity in vivo. Immortalized mesothelial cells from wildtype (iMeso-WT1), from NF2+/- heterozygous (iMeso-NF3) mice and the NF2+/- mouse-derived mesothelioma cell line RN5 were used to compare acute cytotoxicity between novel silica-based manufactured nanoparticles (MNP) and crocidolite. All cell lines were sensitive to crocidolite-induced cytotoxicity, but rather resistant to the spherical MNP, with iMeso-NF3 being the most sensitive and RN5 being the least sensitive cells. Chronic exposure (1 month) of iMeso-NF3 cells to a sub-lethal dose of crocidolite resulted in increased acute resistance to crocidolite. Yet, asbestos-resistant iMeso-NF3 cells didn't induce tumors after intraperitoneal injection, while RN5 cell injection resulted in macroscopic tumors after 5 weeks. Thus, mouse mesothelium-derived cell lines appear well suited to study potential hazardous health effects of MNP.

Keywords


In Vitro Mesothelium Model, NF2, Mesothelial Cells, Asbestos, RN5, Silica Particles.

References





DOI: https://doi.org/10.22506/ti%2F2016%2Fv23%2Fi2%2F146699