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

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.