Evaluation of Genotoxicity of Nanoparticles in Mouse Models

Owing to new and unique properties, engineered nanoparticles (NPs) likely pose different risks than their constituent chemicals and these risks need to be understood. In particular, it is important to assess genotoxicity, since genotoxicity is a precursor to carcinogenicity. Here we describe a battery of tests for the assessment of genotoxicity of NPs in vivo in mice. Mice can be exposed to NPs for various exposure durations and by any route of exposure, provided NPs are absorbed into the systemic blood circulation. The testing battery measures three well-established markers of DNA damage: oxidative DNA damage, double strand breaks (DSBs) and chromosomal damage. These markers are measured in peripheral blood cells by microscopic techniques. 8-oxo-7,8-dihydro-2-deoxyguanine (8-oxoG), indicative of oxidative DNA damage, and phosphorylated histone 2AX (γ-H2AX) foci, indicative of DSBs, are determined in white blood cells by immunofluorescence. Micronuclei, indicative of chromosomal damage, are examined in erythrocytes on Giemsa-stained peripheral blood smears. This testing battery can be easily integrated in general toxicology studies or studies examining carcinogenic potential of NPs.