Impact of copper oxide particle dissolution on lung epithelial cell toxicity: response characterization using global transcriptional analysis

The in vitro and vivo toxicity of copper oxide nanoparticles (CuO NPs) is attributed to both particle dissolved ion species. However, a clear understanding (1) the specific cellular responses that are modulated by two species (2) temporal dynamics toxicity, as proportional amount particulate ionic forms change over time, lacking. In current study, microparticulate CuO MPs), NPs, Cu2+ were characterized order elucidate ion-induced kinetic effects. Particle dissolution experiments carried out relevant cell culture medium, using NPs MPs. Mouse lung epithelial cells exposed for 2–48 h with 1–25 µg/mL MPs, or 7 54 CuCl2. Cellular viability genome-wide transcriptional assessed. Dose time-dependent cytotoxicity observed NP cells, which was delayed subtle CuCl2 not MPs treated cells. Analyses differentially expressed genes associated pathway perturbations showed ions released extracellular medium insufficient account potency cytotoxicity. Further organization gene expression results an Adverse Outcome Pathway (AOP) framework revealed series key events potentially involved toxicity. AOP applicable induced metal varying solubility, thus, can facilitate development alternative strategies screen their