PUBLICATION

Diastereoisomer-specific effects of hexabromocyclododecanes on hepatic aryl hydrocarbon receptors and cytochrome P450s in zebrafish (Danio rerio)

Authors
Du, M., Fang, C., Qiu, L., Dong, S., Zhang, X., Yan, C.
ID
ZDB-PUB-150317-10
Date
2015
Source
Chemosphere   132: 24-31 (Journal)
Registered Authors
Keywords
Aryl hydrocarbon receptor, Cytochrome P450, Diastereoisomer, Hexabromocyclododecane
MeSH Terms
  • Animals
  • Cytochrome P-450 CYP1A1/metabolism
  • Cytochrome P-450 Enzyme System/metabolism*
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Cytochrome P-450 CYP1B1
  • Receptors, Aryl Hydrocarbon/metabolism*
  • Liver/metabolism
  • Hydrocarbons, Brominated/adverse effects*
PubMed
25770833 Full text @ Chemosphere
Abstract
In order to elucidate the mechanism for diastereoisomer-specific toxicity and metabolism of hexabromocyclododecanes (HBCDs) in biota, zebrafish (Danio rerio) were exposed to different concentrations of individual HBCD diastereoisomers (α-, β- and γ-HBCD) in water for 7 and 21d. We examined the gene expression of aryl hydrocarbon receptor (AHR) and cytochrome P450 (CYP), as well as ethoxyresorufin-O-deethylase (EROD) activity in zebrafish livers. Exposure to different HBCD diastereoisomers caused different expression of AHRs in zebrafish livers. For instance, 10 and 100μgL(-1) of α- and β-HBCD up-regulated the expressions of ahr1a and ahr1b in zebrafish liver, whereas 10 and 100μgL(-)(1) of γ-HBCD down-regulated them after 7d exposure. α-HBCD showed the most significant up-regulation of ahr1a and ahr1b expression, whereas γ-HBCD showed the most significant down-regulation of their expression among three HBCD diastereoisomers. Moreover, HBCDs could affect the expression of CYP1s as well as EROD activity in a gene-specific and diastereoisomer-specific manner. α-, β- and γ-HBCD inhibited cyp1a expression but enhanced the expression of cyp1b1 and cyp1c1. α-, β- and γ-HBCD showed different degrees of effect on the same CYP1 gene in a concentration-dependent way. The different effects of HBCD diastereoisomers on these genes we examined and EROD activity not only indicate diastereoisomer-specific toxic effect, but also in turn explain diastereoisomer-specific accumulation of HBCDs in zebrafish.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping