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

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.