Nano-titanium dioxide induces genotoxicity and apoptosis in human lung cancer cell line, A549

The increased inhaled application of titanium dioxide nanoparticles (TiO2 NPs) increases the potential pulmonary health risks. The present investigations were carried out to study the TiO2 NPs-induced apoptosis, oxidative stress and genotoxicity in the human lung cancer cell line, A549, a widely used cell system for pulmonary toxicity studies. Tetrazolium bromide salt and lactate dehydrogenase release assays were used to study the cytotoxicity. The genotoxicity studies were carried out using cytokinesis block micronucleus assay. Apoptosis was confirmed by the formation of apoptotic bodies and altered expression (messenger RNA (mRNA) and protein) of markers such as P⁵³, P²¹, Bax, Bcl2 and cleaved caspase-3. Cells exposed to TiO ₂ NPs (10 and 50 μg/ml) for 6-24 h shows significant induction in oxidative stress, that is, the production of reactive oxygen species and malondialdehyde and decrease in the activity of catalase and glutathione. TiO₂ NPs exposure also induces the formation of apoptotic bodies and micronucleus as marker of genotoxicity. A significant up-regulation in the expression of apoptosis markers such as P⁵³, P²¹ and cleaved caspase-3 was observed, while the levels were down-regulated for Bcl₂ at both mRNA and protein levels. TiO₂ NPs exposure could not pose significant effects on Bax expression. Data indicate that nano-TiO₂ induces oxidative stress, genotoxicity and apoptosis in human lung cancer cell line, A549. Our result also identifies the mechanisms involved in TiO₂ NP-induced changes in A549 cells. Perhaps, reporting for the first time, the association of TiO₂ NPs-induced genotoxicity and apoptosis at transcriptional and translational level in the human lung cancer cell line, A549 cells.