title: 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).
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.
authors.affiliation: Man-Technology-Environment Research Centre (MTM), School of Science and Technology, Örebro University, Fakultetsgatan 1, S-701 82 Örebro, Sweden. Electronic address: melanie.blanc@oru.se.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Blanc
authors.affiliation: Man-Technology-Environment Research Centre (MTM), School of Science and Technology, Örebro University, Fakultetsgatan 1, S-701 82 Örebro, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Kärrman
authors.affiliation: Man-Technology-Environment Research Centre (MTM), School of Science and Technology, Örebro University, Fakultetsgatan 1, S-701 82 Örebro, Sweden.
authors.forename: Petr
authors.initials: P
authors.lastname: Kukucka
authors.affiliation: Örebro Life Science Centre, School of Science and Technology, Örebro University, Fakultetsgatan 1, S-701 82 Örebro, Sweden.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Scherbak
authors.affiliation: Man-Technology-Environment Research Centre (MTM), School of Science and Technology, Örebro University, Fakultetsgatan 1, S-701 82 Örebro, Sweden.
authors.forename: Steffen
authors.initials: S
authors.lastname: Keiter
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D002208:Caproates / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D005466:Fluorocarbons / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000235:genetics*
chemical_list: D017738:Alkanesulfonic Acids; D002208:Caproates; D005466:Fluorocarbons; D014874:Water Pollutants, Chemical; C076994:perfluorooctane sulfonic acid; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl; C479228:perfluorohexanoic acid
keywords: Lipids; Mixture toxicity; Molecular pathway; PFAS; Zebrafish; cyp1a