Investigation of the genotoxic potential of nanomaterials is essential to evaluate if they pose a
cancer risk for exposed workers and consumers. The Chinese hamster ovary cell line CHO-K1 is recommended by the OECD for use in the micronucleus assay and is commonly used for genotoxicity testing. However, studies investigating if this cell line is suitable for the genotoxic evaluation of nanomaterials, including induction of
DNA adduct and micronuclei formation, are rare and for
silver nanoparticles (Ag NPs) missing. Therefore, we here systematically investigated
DNA and chromosomal damage induced by BSA coated Ag NPs (15.9±7.6 nm) in CHO-K1 cells in relation to cellular uptake and intracellular localization, their effects on mitochondrial activity and production of
reactive oxygen species (ROS), cell cycle, apoptosis and
necrosis. Ag NPs are taken up by CHO-K1 cells and are presumably translocated into endosomes/lysosomes. Our cytotoxicity studies demonstrated a concentration-dependent decrease of mitochondrial activity and increase of intracellular
reactive oxygen species (ROS) in CHO-K1 cells following exposure to Ag NPs and Ag⁺ (0-20 μg/ml) for 24h.
Annexin V/
propidium iodide assay showed that Ag NPs and Ag⁺ induced apoptosis and
necrosis, which is in agreement with an increased fraction of cells in subG1 phase of the cell cycle. Genotoxicity studies showed that Ag NPs but also
silver ions (Ag⁺) induced bulky-
DNA adducts,
8-oxodG and micronuclei formation in a concentration-dependent manner, however, there were quantitative and qualitative differences between the particulate and ionic form of
silver. Taken together, our multi-platform genotoxicity and cytotoxicity analysis demonstrates that CHO-K1 cells are suitable for the investigation of genotoxicity of nanoparticles like Ag NPs.