RT Journal Article SR Electronic T1 Titanium Dioxide Nanoparticles Induce DNA Damage and Genetic Instability In vivo in Mice JF Cancer Research JO Cancer Res FD American Association for Cancer Research SP 8784 OP 8789 DO 10.1158/0008-5472.CAN-09-2496 VO 69 IS 22 A1 Trouiller, Benedicte A1 Reliene, Ramune A1 Westbrook, Aya A1 Solaimani, Parrisa A1 Schiestl, Robert H. YR 2009 UL http://cancerres.aacrjournals.org/content/69/22/8784.abstract AB Titanium dioxide (TiO2) nanoparticles are manufactured worldwide in large quantities for use in a wide range of applications including pigment and cosmetic manufacturing. Although TiO2 is chemically inert, TiO2 nanoparticles can cause negative health effects, such as respiratory tract cancer in rats. However, the mechanisms involved in TiO2-induced genotoxicity and carcinogenicity have not been clearly defined and are poorly studied in vivo. The present study investigates TiO2 nanoparticles–induced genotoxicity, oxidative DNA damage, and inflammation in a mice model. We treated wild-type mice with TiO2 nanoparticles in drinking water and determined the extent of DNA damage using the comet assay, the micronuclei assay, and the γ-H2AX immunostaining assay and by measuring 8-hydroxy-2′-deoxyguanosine levels and, as a genetic instability endpoint, DNA deletions. We also determined mRNA levels of inflammatory cytokines in the peripheral blood. Our results show that TiO2 nanoparticles induced 8-hydroxy-2′-deoxyguanosine, γ-H2AX foci, micronuclei, and DNA deletions. The formation of γ-H2AX foci, indicative of DNA double-strand breaks, was the most sensitive parameter. Inflammation was also present as characterized by a moderate inflammatory response. Together, these results describe the first comprehensive study of TiO2 nanoparticles–induced genotoxicity in vivo in mice possibly caused by a secondary genotoxic mechanism associated with inflammation and/or oxidative stress. Given the growing use of TiO2 nanoparticles, these findings raise concern about potential health hazards associated with TiO2 nanoparticles exposure. [Cancer Res 2009;69(22):8784–9]©2009 American Association for Cancer Research.