Size‐dependent cytotoxicity and genotoxicity of ZnO particles to human lymphoblastoid (WIL2‐NS) cells

The relationship between particle size and cytogenotoxicity of ZnO particles was systematically studied in vitro using WIL2‐NS human lymphoblastoid cells. Before toxicity measurements, the ZnO particles of three different sizes (26 nm, 78 nm, and 147 nm) were well characterized for their physical and chemical properties to ensure that variations in other properties including surface chemistry and particle shape, which also may influence particle toxicity, were minimal. Cell viability testing showed that increasing cytotoxicity was associated with decreasing particle size. Both the dissolution kinetics of ZnO particles in supplemented cell culture medium and the apparent numbers of ZnO particles internalized by cells were size dependent and showed strong correlation with cytotoxicity. Genotoxicity, as measured by micronucleus formation, was significantly enhanced in the presence of the medium‐sized and large‐sized particles. The observation that necrosis increased with smaller‐ sized particles but micronuclei were present to a greater extent with larger‐ sized particles suggests that different mechanisms of cell damage induction or susceptibilities are operating depending on particle size. Environ. Mol. Mutagen. 56:767–776, 2015. © 2015 Wiley Periodicals, Inc.