UNASSIGNED: @entity6701 nanoparticles ( @entity3759 -NPs) are one of the most produced NPs in the world. Their @entity137 has been studied for a decade using acute exposure scenarios, i.e. high exposure concentrations and short exposure times. In the present study, we evaluated their genotoxic impact using long-term and low concentration exposure conditions. A549 alveolar epithelial cells were continuously exposed to 1-50   g/mL @entity3759 -NPs, 86% anatase/14% rutile, 24  6 nm average primary diameter, for up to two months. Their @entity137 , oxidative potential and intracellular accumulation were evaluated using @entity98 assay and reactive @entity26 species measurement, transmission electron microscopy observation, micro-particle-induced X-ray emission and inductively-coupled plasma mass spectroscopy. Genotoxic impact was assessed using alkaline and Fpg-modified comet assay, immunostaining of @entity15664 foci and the cytokinesis-blocked micronucleus assay. Finally, we evaluated the impact of a subsequent exposure of these cells to the alkylating agent @entity10842 . We demonstrate that long-term exposure to @entity3759 -NPs does not affect cell viability but causes DNA damage, particularly oxidative damage to DNA and increased @entity15664 foci counts, correlated with increased intracellular accumulation of NPs. In addition, exposure over 2 months causes cellular responses suggestive of adaptation, characterized by decreased proliferation rate and stabilization of @entity3759 -NP intracellular accumulation, as well as sensitization to @entity10843 . Taken together, these data underline the genotoxic impact and sensitization effect of long-term exposure of lung alveolar epithelial cells to low levels of @entity3759 -NPs.

Long-term exposure of A549 cells to XXXX nanoparticles induces DNA damage and sensitizes cells towards genotoxic agents.

@entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'cytotoxicity'] @entity10842 :: ('MESH:D008741', 'Chemical') :: ['methyl methanesulfonate'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity98 :: ('CHEBI:53233', 'Chemical') :: ['MTT'] @entity15664 :: ('7158', 'Gene') :: ['53BP1'] @entity6701 :: ('MESH:C009495', 'Chemical') :: ['Titanium dioxide'] @entity10843 :: ('CHEBI:25255', 'Chemical') :: ['MMS'] @entity3759 :: ('CHEBI:32234', 'Chemical') :: ['TiO2']
@entity6701 :: (MESH:C009495,Chemical) :: ['titanium dioxide']
