Shelterin differentially respond to oxidative stress induced by TiO2-NPs and regulate telomere length in human hepatocytes and hepatocarcinoma cells in vitro

Highlights: • Exposed to TiO₂-NPs caused telomere shortening and chromosome instability in normal cells but not in cancer cells. • The shelterin and Nrf-2 of normal and cancer cells differentially respond to oxidative stress induced by TiO₂-NPs. • The upregulation of Nrf-2 and shelterin protect telomere and chromosome stability against TiO₂-NPs exposure. Titanium dioxide nanoparticles (TiO₂-NPs) have raised serious attention for their widely use and potential adverse effects on human mainly due to producing ROS. However, the influence of TiO₂-NPs on telomere maintaining has not been studied clearly. Shelterin plays core roles in telomere length (TL) regulation. Abnormal TL are associated with chromosome instability (CIN) and high risk of diseases. This study investigated whether TiO₂-NPs affect TL to induce CIN through ROS generation and the possible mechanisms. Human hepatocyte L-02 and hepatocarcinoma cells QGY were exposed to TiO₂-NPs (0, 40, 80 μg/mL) for 72 h. The intracellular hydrogen dioxide (H₂O₂) concentration were measured. The TL, Nrf-2, and three core shelterin components (TRF1, TRF2, and POT1) transcription level were determined by quantitative real-time PCR. CIN was measured by cytokinesis-block micronucleus assay. TiO₂-NPs exposure increased intracellular H₂O₂ in both L-02 and QGY cells, and induced Nrf-2, TRF1, TRF2, POT1 downregulated transcription compared with control (P P P P Nrf-2 to oxidative stress induced by TiO₂-NPs led to the weakened telomere protection in normal cells and effective telomere maintenance in cancer cells, respectively. The upregulation of Nrf-2 and shelterin could protect TL and chromosome stability against TiO₂-NPs exposure.