Nanoceria’s Silent Threat: Investigating Acute and Sub-Chronic Effects of CeO2 Nanopowder (≤50 nm) on the Human Intestinal Epithelial Cells

The increased mobilization of Rare Earth Elements (REEs), due to emerging technologies, could impact human health. The study assessed the effects of CeO₂ nanopowder (100 μg/mL) in human intestinal cells (HT-29) following both acute (24 h) and, a novelty for in vitro study, sub-chronic exposure, treating subcultures of exposed cells to CeO₂ NP up to 35 days. Recovery was also examined in exposed cells' progeny. CeO₂ NP internalization and acute cytotoxicity were dose and time dependent. A significant pro-oxidant effect was observed for up to 14 days. The highest mitochondrial impairment was detected after 7 days, but in post-exposure experiments the recovery was observed. Conversely, genotoxicity highlighted the saturation of the DNA repair mechanisms. The irreversible cell damage of sub-chronic exposure was highlighted by the percentage of death cells (<i>p</i> = 0.011) and by the weekly cell replication index (5.68 vs. 7.41). The homeostatic mitophagy pathway was able to counteract ROS-induced mitochondrial dysfunction, as shown by overexpression of ATG5, LC3, and BECN1 genes throughout the examined times. Instead, the overexpression of the pro-apoptotic gene Bax was very brief, highlighting that prolonged exposure might cause more widespread adverse effects, also involving cells that are not directly exposed to nanoceria.