title: Long-term effects and chemosensitizing potential of perfluorinated chemicals (PFCs) in zebrafish (Danio rerio)
creator: Keiter, Susanne
subject: 500
subject: 500 Natural sciences and mathematics
subject: 590
subject: 590 Zoological sciences
description: Increased awareness of the human and environmental health risks associated with perfluorinated chemicals (PFCs) has raised intensive discussions among authorities and policymakers. Yet, despite declined use of PFCs in industrial and consumer products, these emerging contaminants are still being detected in aquatic environments worldwide. In light of the persistent properties of PFCs, fairly little attention has been given to long-term effects. Another challenging topic in the context of PFCs concerns their potential to interact synergistically; a relevant matter given the complex exposure scenarios in aquatic systems.   This thesis aimed at increasing the knowledge and understanding of PFCs and their toxicity towards an aquatic vertebrate model, the zebrafish (Danio rerio). Focus was on multixenobiotic resistance (MXR) and toxicity following chronic exposure. Selected PFCs were evaluated in transporter efflux assays serving to determine the synergistic potential via P-glycoprotein (P-gp) transporter inhibition. Long-term effects following single and binary exposures of perfluorooctane sulfonate (PFOS) and bisphenol A (BPA) were evaluated over two full generations with emphasis on survival, histological alterations, vitellogenin (Vtg) and reproductive success.   Among the tested PFCs, PFOS induced the strongest accumulation of the standard P-gp transporter substrate rhodamine B (RhB) in zebrafish embryos. An up to fourteen-fold RhB-retention was found in PFOS-exposed embryos if compared with control animals. In comparison, the effect of PFOS on the uptake of the P-gp substrate calcein-AM by MDCKII cells overexpressing human P-gp was substantially smaller than that of the reference compound verapamil indicating that PFOS only weakly interacts with human P-gp. In the long-term study, the most prevalent effects following waterborne PFOS-exposure were decreased survival in off-spring generations and hepatocellular alterations. The hypothesis that the presence of PFOS increases the endocrine potential of BPA could not be confirmed in zebrafish.  This thesis provides further evidence of the chemosensitizing potential of some PFCs in zebrafish. Although the exact mechanisms of action behind the increased uptake of P-gp substrates remain unclear, the results obtained further highlight the importance of mixture toxicity when investigating the hazardous potential of PFCs. Adverse long-term effects on liver structure and survival in zebrafish were only seen at concentrations well above ecologically relevant concentrations. Yet, the decline in survival rates following PFOS-exposure seen over generations again documents the necessity of long-term approaches within the assessment of persistent environmental pollutants.  
date: 2013
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/14550/1/PhD%20thesis%20final.pdf
identifier: DOI:10.11588/heidok.00014550
identifier: urn:nbn:de:bsz:16-heidok-145506
identifier:   Keiter, Susanne  (2013) Long-term effects and chemosensitizing potential of perfluorinated chemicals (PFCs) in zebrafish (Danio rerio).  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/14550/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng