Evaluating quinoline's genotoxic potential: A study on hepatocyte oxidative damage and DNA stability

Quinoline is a heterocyclic aromatic compound with ecotoxicity, but the evidence of its toxic effects is insufficient. Through acute exposure of primary hepatocytes, combined with in vitro cytotoxicity and molecular docking simulation, the dual pathway mechanism induced by quinoline: Reactive oxygen species (ROS)-mediated oxidative damage and interaction with DNA was studied. Quinoline exposure led to excessive production of ROS in liver cells, resulting in lipid peroxidation and depletion of antioxidant defenses. Mitochondrial dysfunction intensified the production of ROS, formed a loop of self-amplification, and suppressed the repair ability of DNA. Spectroscopic analysis and molecular docking confirmed that quinoline may stabilize the embedding and binding of quinoline through π-H, H-receptor and hydrophobic force, and enhance the genotoxicity potential. The direct interaction between quinoline and DNA induced oxidative DNA damage and chain breakage, which was verified by ultraviolet spectrum decoloration, fluorescence enhancement and circular dichroism signal change. The above results confirmed that the stability of hepatocyte genome was destroyed, which provided a basis for toxicity evaluation and risk assessment of quinoline analogues.