Polybrominated diphenyl ethers (
PBDEs) had been used extensively in electrical and electronic products as brominated
flame retardants.
PBDEs are widely distributed in environment media and wildlife since they are lipophilic and persistent, resulting in bioaccumulation and bioamplification through food chains. Accumulation of
PBDEs in the environment and human tissues will consequently cause potential negative effects on the ecological environment and human health. To date, some in vitro and in vivo studies have reported that
PBDEs possess neurotoxicity, hepatotoxicity, immunotoxicity, reproduction toxicity, endocrine disrupting activity and carcinogenicity.
BDE-47 is one of the most predominant
PBDE congeners detected in human tissues. The objective of this study is to investigate whether low concentration of
BDE-47 could cause hormesis effect in the human
hepatoma HepG(2) cells, and to explore the possible molecular mechanism. The results showed that low concentration of
BDE-47 (10(-10), 10(-9) and 10(-8) M) could promote cell proliferation and cause no obvious change in DNA damage or cell apoptosis, while the high concentration significantly inhibit cell proliferation. Meanwhile, the
reactive oxygen species (ROS) in low concentration
BDE-47 (10(-10), 10(-9) and 10(-8) M) treated groups significantly elevated compared with the control group. After low concentration
BDE-47 treatment, the expression of
proliferating cell nuclear antigen (
PCNA),
Cyclin D1,
DNA-dependent protein kinase catalytic subunit (
DNA-
PKcs) and phosphorylated
protein kinase B (p-Akt) in the HepG(2) cells was markedly up-regulated. However, in
DNA-
PKcs inhibited cells, the promotion effect on cell proliferation was significantly suppressed. Cell cycle analysis showed a significant decrease in G1 phase after exposure to low concentration of
BDE-47. Moreover, pre-exposure to low concentration
BDE-47 seemed alleviate the negative effects of high concentration (50 μM) exposure to cause DNA damage and apoptosis. These results suggested that
BDE-47 has a hormesis effect in HepG(2) cells and
DNA-
PKcs/Akt pathway may be involved in regulation of cell proliferation and apoptosis.