Cytotoxicity of Typical Diiodoalkanes from Shale Gas Wastewater in HepG2 Cells

Shale gas extraction releases significant quantities of organic iodides of "unknown origin", which generally pose high ecological and health risks, yet their toxic mechanisms remain unclear. In this study, the human hepatocellular carcinoma (HepG2) cell line was employed as an in vitro cell model to assess the cytotoxic effects of three typical organic iodides (1,2-diiodoethane, 1,3-diiodopropane, and 1,4-diiodobutane) identified in shale gas extraction wastewater from Chongqing, China. The results demonstrated that all three diiodoalkanes exhibited significant toxic effects on HepG2 cells at a concentration of 25 µM, and this effect demonstrated a dose-dependent pattern. As the concentration of diiodoalkanes increased, the viability of HepG2 cells decreased significantly, while cell mortality increased markedly. The transcriptomic analysis indicated that exposure to these three diiodoalkanes induced abnormal expression of genes associated with the extracellular space, extracellular matrix (ECM), and endoplasmic reticulum (ER) in HepG2 cells, which was presumed to be linked to the disruption of the intracellular redox-antioxidant system homeostasis by the diiodoalkanes. Furthermore, assays of intracellular reactive oxygen species (ROS) and antioxidant enzyme/molecule levels suggested that diiodoalkane exposure triggered excessive intracellular ROS production, induced oxidative stress, and ultimately resulted in cell death.