Effects of PBDE-47 on cytotoxicity and genotoxicity in human neuroblastoma cells in vitro

Abstract

Polybrominated diphenyl ethers (PBDEs) are an important class of flame retardants. Because of their detection in human breast milk and structural similarity to polychlorinated biphenyls (PCBs), concern has been raised about their potential toxicity, particularly neurotoxic effects in newborns and children. The aim of the current study was to evaluate the cytotoxic and genotoxic effects of 2,2′,4,4′-tetrabromodiphenyl ether (PBDE-47) in human neuroblastoma (SH-SY5Y) cells in vitro. SH-SY5Y cells were incubated with different concentrations of PBDE-47 (1, 2, 4, 8 μg/ml) for 24 h, and a set of bioassays were conducted to measure: cell viability, cell proliferation (nuclear division index, NDI), lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) formation, cell apoptosis, and DNA breakage and cytogenetic damage. The data showed that PBDE-47 inhibited cell viability, increased LDH leakage, and induced cell apoptosis. All significant effects were observed at concentrations of 4 μg/ml and above ( P < 0.05). After 24 h exposure, a concentration-dependent increase in ROS formation was observed, and there were obviously increase in comparison to the control at concentrations as low as 2 μg/ml PBDE-47. Log-transformed Olive Tail Moment (OTM) were significantly increased compared with the control at various PBDE-47 concentrations ( P < 0.05), while a significant increase in the percentage of DNA in the tail was only observed at 8 μg/ml PBDE-47 ( P < 0.05). PBDE-47 caused a concentration-dependent decrease in NDI, and concentration-dependent increases in chromosome abnormalities as measured by total Micronuclei (MNi)/1000 binucleate cells (BNCs), micronucleated binucleate cells (MNBNCs)/1000 BNCs, and nucleoplasmic bridges (NPBs)/1000 BNCs. The results indicate that PBDE-47 is cytotoxic and genotoxic in SH-SY5Y cells in vitro.