Nanoparticle-induced genotoxicity can arise through different mechanisms, and generally, primary and secondary genotoxicity can be distinguished where the secondary is driven by an inflammatory response. It is, however, yet unclear how a secondary genotoxicity can be detected using in vitro methods. The aim of this study was to investigate
inflammation and genotoxicity caused by agglomerated
nickel (Ni) and
nickel oxide (NiO) nanoparticles and, furthermore, to explore the possibility to test secondary (
inflammation-driven) genotoxicity in vitro. As a benchmark particle to compare with, we used crystalline
silica (
quartz). A
proteome profiler antibody array was used to screen for changes in release of 105 different
cytokines and the results showed an increased secretion of various
cytokines including
vascular endothelial growth factor (
VEGF) following exposure of macrophages (differentiated THP-1 cells). Both Ni and NiO caused DNA damage (comet assay) following exposure of human bronchial epithelial cells (HBEC) and interestingly
conditioned media (CM) from exposed macrophages also resulted in DNA damage (2- and 3-fold increase for Ni and NiO, respectively). Similar results were also found when using a co-culture system of macrophages and epithelial cells. In conclusion, this study shows that it is possible to detect a secondary genotoxicity in lung epithelial cells by using in vitro methods based on
conditioned media or co-cultures. Further investigation is needed in order to find out what factors that are causing this secondary genotoxicity and whether such effects are caused by numerous nanoparticles.