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author:

Wang, Liulin (Wang, Liulin.) [1] | Zou, Wen (Zou, Wen.) [2] | Zhong, Yufang (Zhong, Yufang.) [3] | An, Jing (An, Jing.) [4] | Zhang, Xinyu (Zhang, Xinyu.) [5] | Wu, Minghong (Wu, Minghong.) [6] (Scholars:吴明红) | Yu, Zhiqiang (Yu, Zhiqiang.) [7]

Indexed by:

SCIE

Abstract:

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 Cl 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 mu M) 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. (C) 2011 Elsevier Ireland Ltd. All rights

Keyword:

Akt BDE-47 Cyclin D1 DNA-PKcs Hormesis ROS

Community:

  • [ 1 ] [Wang, Liulin]Shanghai Univ, Inst Environm Pollut & Hlth, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China
  • [ 2 ] [Zou, Wen]Shanghai Univ, Inst Environm Pollut & Hlth, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China
  • [ 3 ] [Zhong, Yufang]Shanghai Univ, Inst Environm Pollut & Hlth, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China
  • [ 4 ] [An, Jing]Shanghai Univ, Inst Environm Pollut & Hlth, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China
  • [ 5 ] [Zhang, Xinyu]Shanghai Univ, Inst Environm Pollut & Hlth, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China
  • [ 6 ] [Wu, Minghong]Shanghai Univ, Inst Environm Pollut & Hlth, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China
  • [ 7 ] [Yu, Zhiqiang]Chinese Acad Sci, Guangzhou Inst Geochem, State Key Lab Organ Geochem, Guangzhou 510640, Guangdong, Peoples R China

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Source :

TOXICOLOGY LETTERS

ISSN: 0378-4274

Year: 2012

Issue: 2

Volume: 209

Page: 193-201

3 . 1 4 5

JCR@2012

2 . 9 0 0

JCR@2023

JCR Journal Grade:2

CAS Journal Grade:3

Cited Count:

WoS CC Cited Count: 54

SCOPUS Cited Count: 58

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 1

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