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Developmental toxicity and endocrine disrupting potency of 4-azapyrene, benzo[b]fluorene and retene in the zebrafish Danio rerio

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Publication date

2012-04-01

Authors

Hawliczek, A.
Nota, B.
Cenijn, P.
Kamstra, Jorke H.ORCID 0000-0001-7984-0229ISNI 0000000390327893
Pieterse, B.
Winter, R.ISNI 0000000028252251
Winkens, K.
Hollert, H.
Segner, H.
Legler, JulietteISNI 0000000137441422

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DOI

https://doi.org/10.1016/j.reprotox.2011.11.001

Document Type

Article

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Abstract

This study examined the developmental toxicity of the polycyclic aromatic hydrocarbons (PAHs) 11H-benzo(b)fluorene (BBF) and 4-azapyrene (AP) in comparison to the known teratogen retene. Developmental toxicity assays were performed in zebrafish embryos exposed for 120h. BBF and retene induced a similar dioxin-like phenotype, whereas AP showed distinct effects, particularly craniofacial malformations. Microarray analysis revealed that for BBF and retene, drug metabolism pathways were induced, which were confirmed by subsequent studies of cyp1a gene expression. For AP, microarray analysis revealed the regulation of genes involved in retinoid metabolism and hematological functions. Studies with a panel of CALUX® bioassays to screen for endocrine disrupting activity of the compounds also revealed novel antagonistic effects of BBF and retene on androgen and progesterone receptors. Classification analysis revealed distinct gene expression profiles for both individual and combined PAH exposure. This study highlights the potential health risk of non priority PAHs. © 2011 Elsevier Inc..

Keywords

Cyp1a, Developmental toxicity, Polycyclic aromatic hydrocarbons, Transcriptomics, Zebrafish, 11h benzo[b]fluorene, 4 azapyrene, androgen, dioxin, polycyclic aromatic hydrocarbon derivative, progesterone receptor, retene, retinoid, unclassified drug, animal experiment, animal model, article, bioassay, concentration response, controlled study, cyp1a gene, developmental toxicity, drug mechanism, drug metabolism, EC10, embryo, exposure, gene, gene expression profiling, genetic regulation, health hazard, machine learning, microarray analysis, nonhuman, toxicity testing, vitamin metabolism, zebra fish, SDG 3 - Good Health and Well-being

Citation

Hawliczek, A, Nota, B, Cenijn, P, Kamstra, J, Pieterse, B, Winter, R, Winkens, K, Hollert, H, Segner, H & Legler, J 2012, 'Developmental toxicity and endocrine disrupting potency of 4-azapyrene, benzo[b]fluorene and retene in the zebrafish Danio rerio', Reproductive Toxicology, vol. 33, no. 2, pp. 213-223. https://doi.org/10.1016/j.reprotox.2011.11.001

URI

http://hdl.handle.net/1874/387340