title: Molecular control of TiO₂-NPs toxicity formation at predicted environmental relevant concentrations by Mn-SODs proteins.
abstract: With growing concerns of the safety of nanotechnology, the in vivo 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 sod-2 and sod-3 genes encoding Mn-SODs in animals exposed to small sizes TiO₂-NPs were significantly different from those in animals exposed to large sizes of TiO₂-NPs. sod-2 and sod-3 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.
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing, China.
authors.forename: Yinxia
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Qiuli
authors.initials: Q
authors.lastname: Wu
authors.forename: Yiping
authors.initials: Y
authors.lastname: Li
authors.forename: Meng
authors.initials: M
authors.lastname: Tang
authors.forename: Boping
authors.initials: B
authors.lastname: Ye
authors.forename: Dayong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D049628:Body Size; D017173:Caenorhabditis elegans / Q000187:drug effects*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000502:physiology*; D010316:Particle Size; D012098:Reproduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D014025:Titanium / Q000633:toxicity*; D000099156:Superoxide Dismutase 2
chemical_list: D029742:Caenorhabditis elegans Proteins; D013482:Superoxide Dismutase; D014025:Titanium; D000099156:Superoxide Dismutase 2; C009495:titanium dioxide; C525107:Sod-3 protein, C elegans