Health & Environmental Research Online (HERO)


Print Feedback Export to File
6305866 
Journal Article 
Activation of human nuclear receptors by perfluoroalkylated substances (PFAS) 
Behr, AC; Plinsch, C; Braeuning, A; Buhrke, T 
2020 
Yes 
Toxicology In Vitro
ISSN: 0887-2333
EISSN: 1879-3177 
62 
104700 
English 
Perfluoralkylated substances (PFAS) such as perfluorooctanoic acid (PFOA) or perfluorooctanesulfonic acid (PFOS) are used to produce, e.g., surface coatings with water- and dirt-repellent properties. These substances have been shown to be hepatotoxic in rodents, and the mechanism of action is mostly attributed to the PFAS-mediated activation of the peroxisome proliferator-activated receptor alpha (PPARα). In the present study, we investigated by using luciferase-based reporter gene assays whether PFOA, PFOS and six alternative PFAS can activate, in addition to PPARα, eight other human nuclear receptors. All tested PFAS except for perfluorobutanesulfonic acid (PFBS) were able to activate human PPARα. Perfluoro-2-methyl-3-oxahexanoic acid (PMOH) and 3H-perfluoro-3-[(3-methoxypropoxy) propanoic acid] (PMPP) were weak agonists of human PPARγ. The other human nuclear receptors (PPARδ, CAR, PXR, FXR, LXRα, RXRα and RARα) were not affected by any PFAS tested in this study. Although PMOH was more effective than PFOA in stimulating PPARα in the transactivation assay, it was less effective in stimulating PPARα-dependent target gene expression in human HepG2 hepatocarcinoma cells. Notably, any effect observed in this in vitro study only occurred at concentrations higher than 10 μM of the respective PFAS which is in all cases several magnitudes above the average blood concentration in the Western population. Thus, the results suggest that nuclear receptor activation may only play a minor role in potential PFAS-mediated adverse effects in humans. 
PFAS; PFOA; PFOS; Nuclear receptor; PPAR alpha; Reporter gene assay 
PFAS
• GenX Chemicals (CASRN 13252-13-6 and CASRN 62037-80-3)
     LitSearch Update: GenX - Oct 2019 - Feb 2020
          WoS
          PubMed
• PFBS
     LitSearch: May 2019 - May 2020
          WoS
          PubMed
• PFOA (335-67-1) and PFOS (1763-23-1)
     LitSearch: Feb 2019 - May 2020
          WoS
          PubMed
     Literature Search Update (Apr 2019 - Sep 2020)
          PubMed
          WOS