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

In order to elucidate the mechanism for diastereoisomer-specific toxicity and metabolism of hexabromo-cyclododecanes (HBCDs) in biota, zebrafish (Danio rerio) were exposed to different concentrations of individual HBCD diastereoisomers (alpha-, beta- and gamma-HBCD) in water for 7 and 21 d. 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 100 mu g L-1 of alpha- and beta-HBCD up-regulated the expressions of ahr1a and ahr1b in zebrafish liver, whereas 10 and 100 mu g L-1 of gamma-HBCD down-regulated them after 7 d exposure. alpha-HBCD showed the most significant up-regulation of ahr1a and ahr1b expression, whereas gamma-HBCD showed the most significant down-regulation of their expression among three HBCD diastereoisomers. Moreover, HBCDs could affect the expression of CYP15 as well as EROD activity in a gene-specific and diastereoisomer-specific manner. alpha-, beta- and gamma-HBCD inhibited cyp1a expression but enhanced the expression of cyp1b1 and cyp1c1. alpha-, beta- and gamma-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. (C) 2015 Published by Elsevier Ltd.