Nanoparticles are prevalent in both commercial and medicinal products; however, the contribution of nanomaterials to carcinogenesis remains unclear. We therefore examined the effects of nano-sized titanium dioxide (TiO 2 ) on poorly tumorigenic and nonmetastatic QR-32 fibrosarcoma cells. We found that mice that were cotransplanted subcutaneously with QR-32 cells and nano-sized TiO 2 , either uncoated (TiO 2 ؊1, hydrophilic) or coated with stearic acid (TiO 2 ؊2, hydrophobic), did not form tumors. However, QR-32 cells became tumorigenic after injection into sites previously implanted with TiO 2 ؊1, but not TiO 2 ؊2, and these developing tumors acquired metastatic phenotypes. No differences were observed either histologically or in inflammatory cytokine mRNA expression between TiO 2 ؊1 and TiO 2 ؊2 treatments. However, TiO 2 ؊2, but not TiO 2 ؊1, generated high levels of reactive oxygen species (ROS) in cell-free conditions. Although both TiO 2 ؊1 and TiO 2 ؊2 resulted in intracellular ROS formation, TiO 2 ؊2 elicited a stronger response, resulting in cytotoxicity to the QR-32 cells.
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