PBDEs-induced Toxicity In Immunocytes And Inhibition Effect On Gap Junctional Intercellular Communication

Polybrominated diphenyl ethers (PBDEs) are a group of organic brominnted flamt retardants. Being widely used in industrial production and daily life, PBDEs have been detected in sorts of environmental medias and organisms, which arouse public concern on their ecological toxicity and health hazard. However, reports on toxic mechanism of PBDEs are still limited at present, especially about immunotoxicity and gap junctional intercellular communication. This dissertation presents two parts, focusing on the apoptosis and its mechanism in immunocytes and effects on gap junctional intercellular communication induced by PBDEs.PART I The involvement of ROS overproduction and mitochondrial dysfunction in PBDE-47-induced apoptosis on Jurkat cells2,2',4,4'-Tetrabromodiphenyl ether (PBDE-47), as one of the congeners of polybrominated diphenyl ethers (PBDEs), is widely present and threatens the human health in many aspects. This study aims to investigate the toxic effects of PBDE-47 on cell viability, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) of Jurkat cells in vitro, and examine the role of ROS and MMP as well as their interaction in the apoptotic process. The results showed that PBDE-47 significantly inhibited the viability of Jurkat cells in a dose-dependent manner by alamar blue assay. Significant induction of apoptosis was detected in Jurkat cells at 25-100μM by Hoechst 33258 and propidium iodide staining, accompanied with overproduction of ROS and downregulation of MMP. Furthermore, N-acetyl-L-cysteine (NAC), a widely-used ROS scavenger, significantly reduced the PBDE-47-induced apoptosis by decreasing ROS level and mediating recovery of the MMP. In conclusion, the results of this study suggest that PBDE-47 could induce apoptosis in Jurkat cells and ROS and mitochondrial dysfunction play important roles in the apoptotic process.PART II Effects of polybrominated diphenyl ethers on gap junctional intercellular communication in HL-7702 cells and mouse skin fibroblastsThe effects of polybrominated diphenyl ethers (PBDEs) on gap junctional intercellular communication(GJIC) in human liver HL-7702 cells and mouse skin fibroblasts were investigated by using scrape loading and dye transfer (SLDT) method. The results showed that both PBDE-47 and PBDE-209 could inhibit the GJIC in human liver HL-7702 cells significantly at 10-50μmol/L with a dose-dependent manner. In mouse skin fibroblasts, PBDE-47 inhibited GJIC at 3.75-50μmol/L and PBDE-209 at 15-50μmol/L. The inhibition efficiency of PBDE-47 was higher than PBDE-209 in both cell lines. The recovery of GJIC was observed after removal of tested chemicals. These results suggest PBDEs can inhibit GJIC, which provides scientific basis for future study about mechanism of toxicity induced by PBDEs.