Journal Article

Gene Expression in Liver Injury Caused by Long-term Exposure to Titanium Dioxide Nanoparticles in Mice

Yaling Cui, Huiting Liu, Yuguan Ze, Zhang Zengli, Yuanyuan Hu, Zhe Cheng, Jie Cheng, Renping Hu, Guodong Gao, Ling Wang, Meng Tang and Fashui Hong

in Toxicological Sciences

Volume 128, issue 1, pages 171-185
Published in print July 2012 | ISSN: 1096-6080
Published online July 2012 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfs153
Gene Expression in Liver Injury Caused by Long-term Exposure to Titanium Dioxide Nanoparticles in Mice

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Although liver toxicity induced by titanium dioxide nanoparticles (TiO2 NPs) has been demonstrated, very little is known about the molecular mechanisms of multiple genes working together underlying this type of liver injury in mice. In this study, we used the whole-genome microarray analysis technique to determine the gene expression profile in the livers of mice exposed to 10 mg/kg body weight TiO2 NPs for 90 days. The findings showed that long-term exposure to TiO2 NPs resulted in obvious titanium accumulation in the liver and TiO2 NP aggregation in hepatocyte nuclei, an inflammatory response, hepatocyte apoptosis, and liver dysfunction. Furthermore, microarray data showed striking changes in the expression of 785 genes related to the immune/inflammatory response, apoptosis, oxidative stress, the metabolic process, response to stress, cell cycle, ion transport, signal transduction, cell proliferation, cytoskeleton, and cell differentiation in TiO2 NP–exposed livers. In particular, a significant reduction in complement factor D (Cfd) expression following long-term exposure to TiO2 NPs resulted in autoimmune and inflammatory disease states in mice. Therefore, Cfd may be a potential biomarker of liver toxicity caused by TiO2 NPs exposure.

Keywords: titanium dioxide nanoparticles; mice; liver; gene expression profiling; inflammation; apoptosis; titanium dioxide nanoparticles

Journal Article.  8270 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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