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HERO ID
3350502
Reference Type
Journal Article
Title
The "adaptive responses" of low concentrations of HBCD in L02 cells and the underlying molecular mechanisms
Author(s)
An, J; Guo, P; Shang, Y; Zhong, Y; Zhang, X; Yu, Y; Yu, Z
Year
2016
Is Peer Reviewed?
Yes
Journal
Chemosphere
ISSN:
0045-6535
EISSN:
1879-1298
Volume
145
Page Numbers
68-76
Language
English
PMID
26688241
DOI
10.1016/j.chemosphere.2015.11.071
Web of Science Id
WOS:000369196300009
Abstract
This study aimed to investigate the "adaptive responses" of hexabromocyclododecanes (HBCD) at environmentally relevant concentrations in human hepatocytes L02. L02 cells were pre-treated with low concentrations of HBCD (10(-13)-10(-11) M), followed by treatment with high concentrations of HBCD, α-hexachlorocyclohexane (α-HCH), polychlorinated biphenyls (PCBs), or polybrominated diphenyl ether-47 (BDE47). The results showed that the pre-treatment with low concentrations of HBCD induced "adaptive responses" to high concentrations of HBCD/α-HCH exposure (but not to PCBs and BDE47), as evidenced by attenuation of survival inhibition, reactive oxygen species (ROS) over-production, and deoxyribonucleic acid (DNA) damage induction. The "adaptive responses" induced by low concentrations of HBCD, which depended on the activation of the phosphatidylinositide 3-kinase/protein kinase B (PI3K/Akt) pathway, reduced the phosphorylation of adenosine monophosphate-activated kinase (AMPK) and enhanced the phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK). The observations were further confirmed by the experiments with inhibitors. Moreover, the evaluation on the changes of metabolic enzymes revealed that HBCD and α-HCH shared a similar pattern of cytochrome P450 induction (CYP2B6), which was different from those of PCBs and BDE47 (CYP1A1 and CYP2B6). These results indicated that low concentrations of HBCD could induce "adaptive responses" to the subsequent treatment with high concentrations of HBCD/α-HCH in L02 cells, which was associated with the PI3K/Akt pathway, and AMPK and p38 MAPK signaling. The "adaptive responses" seemed to be dependent on the types of chemicals in terms of the metabolic patterns and chemical structures.
Keywords
HBCD; PI3K/Akt pathway; AMPK; p38 MAPK; L02 cells
Tags
IRIS
•
Hexabromocyclododecane (HBCD)
New 7/2016 (private)
Database Searches
Pubmed
Sources of Mechanistic and Toxicokinetic Data
Mechanistic and genotoxicity studies
•
PCBs
Supplemental
Litsearches
Litsearch Aug 2015 - Aug 2016
Pubmed
OPPT REs
•
OPPT_Cyclic Aliphatic Bromine Cluster (HBCD)_C. Engineering
Data screening total
Screening: Excluded
•
OPPT_Cyclic Aliphatic Bromine Cluster (HBCD)_D. Exposure
Total – title/abstract screening
Off topic
•
OPPT_Cyclic Aliphatic Bromine Cluster (HBCD)_E. Fate
Total – title/abstract screening
Off topic
•
OPPT_Cyclic Aliphatic Bromine Cluster (HBCD)_F. Human Health
Total – title/abstract screening
On topic
Peer review
Primary source
Cited in IRIS document or IRIS HERO page
On topic - additional tags for titles/abstracts
MOA
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