Effects of perfluorooctanoate and perfluorooctane sulfonate exposure on hepatoma Hep G2 cells.
Perfluorinated compounds (PFCs) are emerging compounds of concern. They are widely distributed in the environment, wildlife and human. Concern has been raised over their possible adverse effects on human health. This study was designed to determine cytotoxic effects of two important PFCs, perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), in a single and a mixture of them exposure to Hep G2 cells. The results showed that PFOA and PFOS (50-200 micromol/l) induced production of reactive oxygen species (ROS), dissipation of mitochondria membrane potential and apoptosis of Hep G2 cells. Moreover, activities of superoxide dismutase, catalase and glutathione reductase were increased, whereas activities of glutathione-S-transferase and glutathione peroxidase were decreased. Glutathione content was reduced. Differential expression of genes, such as p53, Bcl-2, caspase-9, was evident in PFOA or PFOS exposure groups. The possible mechanism was that they could overwhelm homeostasis of antioxidative systems, boost ROS generation, impact mitochondria, and affect genes expression of apoptotic regulators, which resulted in start-ups of apoptosis program. Cells exposed to mixture of PFOA and PFOS and each of them showed non-apoptotic rate significant difference, which indicated that the combined effect of two compounds was summation effect, but neither synergistic nor antagonistic effect.
Hu
Xiao-Zhong
XZ
Technology Center of Hubei Entry-Exit Inspection and Quarantine Bureau of PRC, Wuhan, People's Republic of China. huxz2002@163.com
Hu
De-Cong
DC
D017738:Alkanesulfonic Acids / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002210:Caprylates / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004785:Environmental Pollutants / Q000633:toxicity*; D005466:Fluorocarbons / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D017738:Alkanesulfonic Acids; D002210:Caprylates; D004396:Coloring Agents; D004785:Environmental Pollutants; D005466:Fluorocarbons; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; C022616:thiazolyl blue