Abstract
Iodide organic compounds, the conversion reaction by-products in shale gas wastewater, have potential risks to ecological environment and human health. However, information about their negative effects and molecular mechanism remains limited. In this study, three typical iodoalkanes (C(2)H(5)I, C(2)H(4)I(2), and C(3)H(6)I(2)) identified in shale gas wastewater from Chongqing of China were utilized to investigate their cytotoxicity and potential mechanisms in Hela cells. Results showed that three iodoalkanes reduced cell proliferation in a dose-dependent manner, and cytotoxicity of di-iodoalkanes (C(2)H(4)I(2) and C(3)H(6)I(2)) was stronger than that of mono-iodoalkanes (C(2)H(5)I). Furthermore, C(2)H(4)I(2) and C(3)H(6)I(2) significantly decreased colony formation of HeLa cells, accompanying by disorder of cell cycle checkpoint genes (CyclinA2, CyclinD1, CyclinE1, CDK2 and p21). Three iodoalkanes stimulated production of intracellular ROS, caused GSH/GSSG ratio decrease, MMP loss, and promoted expression of NRF2, HO-1 and NQO-1. Additionally, C(2)H(4)I(2) and C(3)H(6)I(2) induced cell membrane damage, cell apoptosis and enhanced expression of apoptosis markers (Caspase-3, Caspase-8, Cyt-c, and p53). Combined use of antioxidant NAC obviously alleviated the toxic effects of iodoalkanes, including cell proliferation inhibition, oxidative stress and apoptosis induction. Generally, iodoalkanes might suppress cell proliferation via inhibiting cycle progression from G(1) to S phase, inducing mitochondrial apoptosis, which was closely related to oxidative stress-mediated mitochondrial damage.