PMID- 34974025
OWN - NLM
STAT- MEDLINE
DCOM- 20220216
LR  - 20220216
IS  - 1879-1026 (Electronic)
IS  - 0048-9697 (Linking)
VI  - 814
DP  - 2022 Mar 25
TI  - Single PFAS and PFAS mixtures affect nuclear receptor- and oxidative 
      stress-related pathways in precision-cut liver slices of Atlantic cod (Gadus 
      morhua).
PG  - 152732
LID - S0048-9697(21)07811-6 [pii]
LID - 10.1016/j.scitotenv.2021.152732 [doi]
AB  - The aim of the present study was to investigate effects of per- and 
      polyfluoroalkyl substances (PFAS), both single compounds and a mixture of these, 
      using precision-cut liver slices (PCLS) from Atlantic cod (Gadus morhua). PCLS 
      were exposed for 48 h to perfluorooctane sulfonate (PFOS), perfluorooctanoate 
      (PFOA) and perfluorononanoate (PFNA) (10, 50 and 100 muM), and three mixtures of 
      these at equimolar concentrations (10, 50 and 100 muM). Transcriptomic responses 
      were assessed using RNA sequencing. Among exposures to single PFAS, PFOS produced 
      the highest number of differentially expressed genes (DEGs) compared to PFOA and 
      PFNA (86, 25 and 31 DEGs, respectively). Exposure to the PFAS mixtures resulted 
      in a markedly higher number of DEGs (841). Clustering analysis revealed that the 
      expression pattern of the PFAS mixtures were more similar to PFOS compared to 
      PFOA and PFNA, suggesting that effects induced by the PFAS mixtures may largely 
      be attributed to PFOS. Pathway analysis showed significant enrichment of pathways 
      related to oxidative stress, cholesterol metabolism and nuclear receptors in 
      PFOS-exposed PCLS. Fewer pathways were significantly enriched following PFOA and 
      PFNA exposure alone. Significantly enriched pathways following mixture exposure 
      included lipid biosynthesis, cancer-related pathways, nuclear receptor pathways 
      and oxidative stress-related pathways such as ferroptosis. The expression of most 
      of the genes within these pathways was increased following PFAS exposure. 
      Analysis of non-additive effects in the 100 muM PFAS mixture highlighted genes 
      involved in the antioxidant response and membrane transport, among others, and 
      the majority of these genes had synergistic expression patterns in the mixture. 
      Nevertheless, 90% of the DEGs following mixture exposure showed additive 
      expression patterns, suggesting additivity to be the major mixture effect. In 
      summary, PFAS exposure promoted effects on cellular processes involved in 
      oxidative stress, nuclear receptor pathways and sterol metabolism in cod PCLS, 
      with the strongest effects observed following PFAS mixture exposure.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Dale, Karina
AU  - Dale K
AD  - Department of Biological Sciences, University of Bergen, Thormohlensgate 53B, 
      5006 Bergen, Norway. Electronic address: karina.dale@stim.no.
FAU - Yadetie, Fekadu
AU  - Yadetie F
AD  - Department of Biological Sciences, University of Bergen, Thormohlensgate 53B, 
      5006 Bergen, Norway. Electronic address: Fekadu.Yadetie@uib.no.
FAU - Horvli, Torill
AU  - Horvli T
AD  - Department of Biological Sciences, University of Bergen, Thormohlensgate 53B, 
      5006 Bergen, Norway.
FAU - Zhang, Xiaokang
AU  - Zhang X
AD  - Department of Molecular Oncology, Institute for Cancer Research, Oslo University 
      Hospital-Radiumhospitalet, Vestenghaugen 8, 0379 Oslo, Norway. Electronic 
      address: Xiaokang.Zhang@rr-research.no.
FAU - Froysa, Havard Guldbrandsen
AU  - Froysa HG
AD  - Institute of Marine Research, Nordnesgaten 50, NO-5005 Bergen, Norway. Electronic 
      address: haavard.guldbrandsen.froeysa@hi.no.
FAU - Karlsen, Odd Andre
AU  - Karlsen OA
AD  - Department of Biological Sciences, University of Bergen, Thormohlensgate 53B, 
      5006 Bergen, Norway. Electronic address: Odd.Karlsen@uib.no.
FAU - Goksoyr, Anders
AU  - Goksoyr A
AD  - Department of Biological Sciences, University of Bergen, Thormohlensgate 53B, 
      5006 Bergen, Norway. Electronic address: anders.goksoyr@uib.no.
LA  - eng
PT  - Journal Article
DEP - 20211231
PL  - Netherlands
TA  - Sci Total Environ
JT  - The Science of the total environment
JID - 0330500
RN  - 0 (Alkanesulfonic Acids)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Fluorocarbons)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
SB  - IM
MH  - *Alkanesulfonic Acids/metabolism/toxicity
MH  - Animals
MH  - *Environmental Pollutants/metabolism
MH  - *Fluorocarbons/analysis
MH  - *Gadus morhua/genetics
MH  - Liver/chemistry
MH  - Oxidative Stress
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
OTO - NOTNLM
OT  - Cholesterol
OT  - Ferroptosis
OT  - Fish
OT  - Mixture toxicity
OT  - PFOS
OT  - Perfluoroalkyl acids (PFAA)
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/01/03 06:00
MHDA- 2022/02/17 06:00
CRDT- 2022/01/02 20:21
PHST- 2021/11/04 00:00 [received]
PHST- 2021/12/09 00:00 [revised]
PHST- 2021/12/23 00:00 [accepted]
PHST- 2022/01/03 06:00 [pubmed]
PHST- 2022/02/17 06:00 [medline]
PHST- 2022/01/02 20:21 [entrez]
AID - S0048-9697(21)07811-6 [pii]
AID - 10.1016/j.scitotenv.2021.152732 [doi]
PST - ppublish
SO  - Sci Total Environ. 2022 Mar 25;814:152732. doi: 10.1016/j.scitotenv.2021.152732. 
      Epub 2021 Dec 31.