title: Diastereoisomer-specific effects of hexabromocyclododecanes on hepatic aryl hydrocarbon receptors and cytochrome P450s in zebrafish (Danio rerio).
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.
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Du
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Fang
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.
authors.forename: Sijun
authors.initials: S
authors.lastname: Dong
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China. Electronic address: xzhang@iue.ac.cn.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.
authors.forename: Changzhou
authors.initials: C
authors.lastname: Yan
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006842:Hydrocarbons, Brominated / Q000009:adverse effects*; D008099:Liver / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D006842:Hydrocarbons, Brominated; D018336:Receptors, Aryl Hydrocarbon; D029961:Zebrafish Proteins; C089796:hexabromocyclododecane; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1
keywords: Aryl hydrocarbon receptor; Cytochrome P450; Diastereoisomer; Hexabromocyclododecane