Multiple biomarkers of the cytotoxicity induced by BDE-47 in human embryonic kidney cells

Polybrominated diphenyl ethers (PBDEs) are widely used as brominated flame-retardants in a variety of industrial products. Among these PBDEs, 2,2′,4,4′-tetra-bromodiphenyl ether (BDE-47) is one of the most predominant congeners inducing multiple toxicities, including hepatotoxicity, neurotoxicity, cytotoxicity, genotoxicity, carcinogenecity and immunotoxicity in human body. In this study, the cytotoxicity of BDE-47 in human embryonic kidney cells (HEK293) was investigated by a set of bioassays, including cell proliferation, apoptosis, oxidative stress and metabolic responses as well as gene expressions related to apoptosis. Results showed that BDE-47 induced an inverted U-shaped curve of cell proliferation in HEK293 cells from 10−6 to 10−4 M. Cell apoptosis and ROS overproduction were detected at 10−5 M of BDE-47 (p < 0.05). In addition, the expressions of Bcl-2 family-encoding genes (Bad, Hrk and Bcl-2) increased significantly in 10−4 M group (p < 0.05). Metabolic responses indicated that BDE-47 mainly caused disturbance in energy metabolism marked by differentially altered ethanol, glutathione, creatine, aspartate, UDP-glucose and NAD+. The increased lactate/alanine ratios indicated the higher reductive state induced by BDE-47 in all exposures confirmed by the overproduction of ROS.