Molecular Control of TiO₂-NPs Toxicity Formation at Predicted Environmental Relevant Concentrations by Mn-SODs Proteins

<div><p>With growing concerns of the safety of nanotechnology, the <em>in vivo</em> toxicity of nanoparticles (NPs) at environmental relevant concentrations has drawn increasing attentions. We investigated the possible molecular mechanisms of titanium nanoparticles (Ti-NPs) in the induction of toxicity at predicted environmental relevant concentrations. In nematodes, small sizes (4 nm and 10 nm) of TiO₂-NPs induced more severe toxicities than large sizes (60 nm and 90 nm) of TiO₂-NPs on animals using lethality, growth, reproduction, locomotion behavior, intestinal autofluorescence, and reactive oxygen species (ROS) production as endpoints. Locomotion behaviors could be significantly decreased by exposure to 4-nm and 10-nm TiO₂-NPs at concentration of 1 ng/L in nematodes. Among genes required for the control of oxidative stress, only the expression patterns of <em>sod-2</em> and <em>sod-3</em> genes encoding Mn-SODs in animals exposed to small sizes of TiO₂-NPs were significantly different from those in animals exposed to large sizes of TiO₂-NPs. <em>sod-2</em> and <em>sod-3</em> gene expressions were closely correlated with lethality, growth, reproduction, locomotion behavior, intestinal autofluorescence, and ROS production in TiO₂-NPs-exposed animals. Ectopically expression of human and nematode Mn-SODs genes effectively prevented the induction of ROS production and the development of toxicity of TiO₂-NPs. Therefore, the altered expression patterns of Mn-SODs may explain the toxicity formation for different sizes of TiO₂-NPs at predicted environmental relevant concentrations. In addition, we demonstrated here a strategy to investigate the toxicological effects of exposure to NPs upon humans by generating transgenic strains in nematodes for specific human genes.</p>