PUBLICATION
Microarray analysis reveals a mechanism of phenolic polybrominated diphenylether toxicity in zebrafish
- Authors
- van Boxtel, A.L., Kamstra, J.H., Cenijn, P.H., Pieterse, B., Wagner, J.M., Antink, M., Krab, K., van der Burg, B., Marsh, G., Brouwer, A., and Legler, J.
- ID
- ZDB-PUB-080501-1
- Date
- 2008
- Source
- Environmental science & technology 42(5): 1773-1779 (Journal)
- Registered Authors
- Legler, Juliette
- Keywords
- none
- MeSH Terms
-
- Animals
- Ethers
- Oligonucleotide Array Sequence Analysis
- Polybrominated Biphenyls/toxicity*
- Zebrafish
- PubMed
- 18441834 Full text @ Env. Sci. Tech.
Citation
van Boxtel, A.L., Kamstra, J.H., Cenijn, P.H., Pieterse, B., Wagner, J.M., Antink, M., Krab, K., van der Burg, B., Marsh, G., Brouwer, A., and Legler, J. (2008) Microarray analysis reveals a mechanism of phenolic polybrominated diphenylether toxicity in zebrafish. Environmental science & technology. 42(5):1773-1779.
Abstract
Polybrominated diphenylethers (PBDEs) are ubiquitous in the environment, with the lower brominated congener 2,2′,4,4′-tetrabromodiphenylether (BDE47) among the most prevalent. The phenolic PBDE, 6-hydroxy-BDE47 (6-OH-BDE47) is both an important metabolite formed by in vivo metabolism of BDE47 and a natural product produced by marine organisms such as algae. Although this compound has been detected in humans and wildlife, including fish, virtually nothing is known of its in vivo toxicity. Here we report that 6-OH-BDE47 is acutely toxic in developing and adult zebrafish at concentrations in the nanomolar (nM) range. To identify possible mechanisms of toxicity, we used microarray analysis as a diagnostic tool. Zebrafish embryonic fibroblast (PAC2) cells were exposed to 6-OH-BDE47, BDE47, and the methoxylated metabolite 6-MeO-BDE47. These experiments revealed that 6-OH-BDE47 alters the expression of genes involved in proton transport and carbohydrate metabolism. These findings, combined with the acute toxicity, suggested that 6-OH-BDE47 causes disruption of oxidative phosphorylation (OXPHOS).Therefore, we further investigated the effect of 6-OH-BDE47 on OXPHOS in zebrafish mitochondria. Results show unequivocally that this compound is a potent uncoupler of OXPHOS and is an inhibitor of complex II of the electron transport chain. This study provides the first evidence of the in vivo toxicity and an important potential mechanism of toxicity of an environmentally relevant phenolic PBDE of both anthropogenic and natural origin. The results of this study emphasize the need for further investigation on the presence and toxicity of this class of polybrominated compounds.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping