PUBLICATION

Mixture-specific gene expression in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonic acid (PFOS), perfluorohexanoic acid (PFHxA) and 3,3',4,4',5-pentachlorobiphenyl (PCB126)

Authors
Blanc, M., Kärrman, A., Kukucka, P., Scherbak, N., Keiter, S.
ID
ZDB-PUB-170312-2
Date
2017
Source
The Science of the total environment   590-591: 249-257 (Journal)
Registered Authors
Keywords
Lipids, Mixture toxicity, Molecular pathway, PFAS, Zebrafish, cyp1a
MeSH Terms
  • Alkanesulfonic Acids/toxicity*
  • Animals
  • Caproates/toxicity*
  • Embryo, Nonmammalian/drug effects*
  • Fluorocarbons/toxicity*
  • Gene Expression Regulation, Developmental/drug effects
  • Polychlorinated Biphenyls/toxicity*
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish/genetics*
PubMed
28283292 Full text @ Sci. Total Environ.
CTD
28283292
Abstract
Perfluorooctane sulfonic acid (PFOS) and 3,3',4,4',5-pentachlorobiphenyl (PCB126) are persistent organic pollutants of high concern because of their environmental persistence, bioaccumulation and toxic properties. Besides, the amphiphilic properties of fluorinated compounds such as PFOS and perfluorohexanoic acid (PFHxA) suggest a role in increasing cell membrane permeability and solubilizing chemicals. The present study aimed at investigating whether PFOS and PFHxA are capable of modifying the activation of PCB126 toxicity-related pathways. For this purpose, zebrafish embryos were exposed in semi-static conditions to 7.5μg/L of PCB126 alone, in the presence of 25mg/L of PFOS, 15.7mg/L of PFHxA or in the presence of both PFOS and PFHxA. Quantitative PCR was performed on embryos aged from 24h post fertilization (hpf) to 96 hpf to investigate expression changes of genes involved in metabolism of xenobiotics (ahr2, cyp1a), oxidative stress (gpx1a, tp53), lipids metabolism (acaa2, osbpl1a), and epigenetic mechanisms (dnmt1, dnmt3ba). Cyp1a and ahr2 expression were significantly induced by the presence of PCB126. However, after 72 and 78h of exposure, induction of cyp1a expression was significantly lower when embryos were co-exposed to PCB126+PFOS+PFHxA when compared to PCB126-exposed embryos. Significant upregulation of gpx1a occurred after exposure to PCB126+PFHxA and to PCB126+PFOS+PFHxA at 30 and 48 hpf. Besides, embryos appeared more sensitive to PCB126+PFOS+PFHxA at 78 hpf: acaa2 and osbpl1a were significantly downregulated; dnmt1 was significantly upregulated. While presented as environmentally safe, PFHxA demonstrated that it could affect gene expression patterns in zebrafish embryos when combined to PFOS and PCB126, suggesting that such mixture may increase PCB126 toxicity. This is of particular relevance since PFHxA is persistent and still being ejected into the environment. Moreover, it provides additional information as to the importance to integrate mixture effects of chemicals in risk assessment and biomonitoring frameworks.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping