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    Low Cytotoxicity of Inorganic Nanotubes and Fullerene-Like Nanostructures in Human Bronchial Epithelial Cells: Relation to Inflammatory Gene Induction and Antioxidant Response

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    The cytotoxicity of tungsten disulfide nano tubes (INT-WS<sub>2</sub>) and inorganic fullerene-like molybdenum disulfide (IF-MoS<sub>2</sub>) nanoparticles (NPs) used in industrial and medical applications was evaluated in comparison to standard environmental particulate matter. The IF-MoS<sub>2</sub> and INT-WS<sub>2</sub> reside in vesicles/inclusion bodies, suggestive of endocytic vesicles. In cells representing the respiratory, immune and metabolic systems, both IF-MoS<sub>2</sub> and INT-WS<sub>2</sub> NPs remained nontoxic compared to equivalent concentrations (up to 100 μg/mL in the medium) of silica dioxide (SiO<sub>2</sub>), diesel engine-derived and carbon black NPs, which induced cell death. Associating with this biocompatibility of IF-MoS<sub>2</sub>\INT-WS<sub>2</sub>, we demonstrate in nontransformed human bronchial cells (NL-20) relative low induction of the pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α. Moreover, IF-MoS<sub>2</sub> and INT-WS<sub>2</sub> activated antioxidant response as measured by the antioxidant response element (ARE) using a luciferase reporter, and induced Nrf2-mediated Phase II detoxification genes. Collectively, our findings suggest that the lower cytotoxicity of IF-MoS<sub>2</sub> and INT-WS<sub>2</sub> NPs does not reflect general biological inertness. Rather, compared to other NP’s, it likely results from decreased pro-inflammatory activation, but a comparable significant capacity to induce protective antioxidant/detoxification defense mechanisms
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