<p>The increasing use of nanoparticles in numerous applications has led to growing concern about their potential toxicological properties. However, the role of epigenetic alterations in toxicity due to nanoparticles remains relatively unexplored. In this study, we examined the effects of ten kinds of nanoparticles on histone modification. We observed that Al₂O₃, CuO or ZnO nanoparticles induced phosphorylation of the histone H2AX at serine 139. In addition, compared with other tested nanoparticles, acetylation of histone H3 lysine 9, 14 and histone H3 (global) caused by CuO and ZnO nanoparticles was most significant. We found that upregulation of histone H3 lysine 27 trimethylation was highly correlated with histone acetylation induced by CuO and ZnO nanoparticles. Furthermore, we proved that CuO or ZnO nanoparticle-induced histone H3 modifications may occur via release of ions from nanoparticles inside cells. We previously showed that phosphorylation of histone H3 at serine 10 can be used to evaluate the toxicity of silver nanoparticles and Ag ion release in combination with detection by side-scattered light from flow cytometry. Our current findings suggest that other histone modifications such as acetylation and methylation of histone H3, may also be good markers for nanoparticle toxicity.</p>