Calcium ions rescue human lung epithelial cells from the toxicity of zinc oxide nanoparticles.
Contradictory results have been reported for in vitro evaluations of whether zinc oxide nanoparticles (ZnO NPs) are cytotoxic. Though there have been reports of ZnO NPs cytotoxicity due to Zn ions released from the nanoparticles, there have also been reports concluding that Zn ions are not cytotoxic. This inconsistency is mostly attributed to the types of cells used. In this research, we investigated the difference in the level of ZnO NPs cytotoxicity due to culturing conditions. The sensitivity of human lung epithelial cells to ZnO NPs cytotoxicity differed depending on the dispersing medium, physiological state of the cells resulting from their growth stage, and composition of the medium. Further, with regard to the toxicity of ZnO NPs, NPs internalized into cells had a greater cytotoxic effect than Zn ions released from ZnO NPs. Instead of inducing cell death, ZnO NPs internalized into cells slowed the rate of cell proliferation. Furthermore, the cytotoxicity of ZnO NPs depended greatly on the concentration of calcium ions (Ca2+) in the medium. When the concentration of Ca2+ was low, the cytotoxicity of ZnO NPs increased markedly. However, the toxicity of ZnO NPs was mitigated by the addition of CaCl2 to the medium. Global gene expression analysis revealed that Ca2+ -induced upregulation of cell cycle functions could be attributable to the mitigation of ZnO NP toxicity by Ca2+.
Nanotechnology Innovation Station, National Institute for Materials Science.
Nobutaka
N
Hanagata
Hiromi
H
Morita
D002122:Calcium Chloride / Q000494:pharmacology; D017610:Calcium Compounds / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D015034:Zinc Oxide / Q000633:toxicity*
D017610:Calcium Compounds; D003470:Culture Media; D017382:Reactive Oxygen Species; D002122:Calcium Chloride; D015034:Zinc Oxide