Replacement per- and polyfluoroalkyl substances (PFAS) are potent modulators of lipogenic and drug metabolizing gene expression signatures in primary human hepatocytes.
Human hepatocytes
Lipids
PFAS
Perfluorinated compounds
Journal
Toxicology and applied pharmacology
ISSN: 1096-0333
Titre abrégé: Toxicol Appl Pharmacol
Pays: United States
ID NLM: 0416575
Informations de publication
Date de publication:
01 05 2022
01 05 2022
Historique:
received:
22
11
2021
revised:
03
03
2022
accepted:
18
03
2022
pubmed:
27
3
2022
medline:
12
4
2022
entrez:
26
3
2022
Statut:
ppublish
Résumé
Per- and polyfluoroalkyl substances (PFAS) are a class of environmental toxicants, and some, such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), have been associated with hepatic steatosis in rodents and monkeys. It was hypothesized that perfluorosulfonic acids (C4, 6, 8), perfluorocarboxylic acids (C4-14), perfluoro(2-methyl-3-oxahexanoic) acid (HFPO-DA), 1H, 1H, 2H, 2H-perfluorooctanesulfonic acid (6:2 FTS) along with 3 PFOS precursors could induce expression of lipid metabolism genes and lipid deposition in human hepatocytes. Five-donor pooled cryopreserved human hepatocytes were cultured and treated with 0.1% DMSO vehicle or various PFAS (0.25 to 25 μM) in media. After a 48-h treatment, mRNA transcripts related to lipid transport, metabolism, and synthesis were measured using a Quantigene Plex assay. After 72-h treatments, hepatocytes were stained with Nile Red dye to quantify intracellular lipids. Overall, PFAS were transcriptionally active at 25 μM. In this model, lipid accumulation was not observed with C8-C12 treatments. Shorter chain PFAS (C4-C5), 6:2 FTS, and PFOS precursor, metFOSA, induced significant liver lipid accumulation, and gene activation at lower concentrations than legacy PFAS. In summary short chain PFAS and other alternative PFAS were more potent gene inducers, and potential health effects of replacement PFAS should be critically evaluated in humans.
Identifiants
pubmed: 35337807
pii: S0041-008X(22)00136-3
doi: 10.1016/j.taap.2022.115991
pmc: PMC9036616
mid: NIHMS1795126
pii:
doi:
Substances chimiques
Alkanesulfonic Acids
0
Fluorocarbons
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
115991Subventions
Organisme : NIEHS NIH HHS
ID : P42 ES027706
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES031080
Pays : United States
Organisme : NIEHS NIH HHS
ID : R15 ES023148
Pays : United States
Organisme : NIEHS NIH HHS
ID : R35 ES031709
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Références
Environ Sci Technol. 2019 Feb 19;53(4):2181-2188
pubmed: 30649875
Environ Int. 2020 Mar;136:105358
pubmed: 32044175
Environ Health Perspect. 2013 Nov-Dec;121(11-12):1313-8
pubmed: 24007715
Environ Toxicol Pharmacol. 2021 Aug;86:103652
pubmed: 33812015
Environ Pollut. 2015 Apr;199:166-73
pubmed: 25660070
Environ Int. 2020 Jan;134:105220
pubmed: 31744629
Toxicol Pathol. 2015 Jun;43(4):558-68
pubmed: 25398757
Arch Toxicol. 2009 Sep;83(9):851-61
pubmed: 19468714
Environ Sci Process Impacts. 2019 Nov 1;21(11):1908-1914
pubmed: 31332417
Biochim Biophys Acta. 2012 Jul;1820(7):1092-101
pubmed: 22484034
Environ Health Perspect. 2013 Mar;121(3):318-23
pubmed: 23308854
Toxicology. 2017 Jul 15;387:95-107
pubmed: 28558994
Environ Health Perspect. 2017 Jul 26;125(7):077018
pubmed: 28749778
Environ Sci Technol. 2016 Jun 21;50(12):6354-62
pubmed: 27192404
J Expo Sci Environ Epidemiol. 2019 Mar;29(2):131-147
pubmed: 30470793
Environ Res. 2015 Jan;136:8-14
pubmed: 25460614
Environ Health Perspect. 2012 May;120(5):655-60
pubmed: 22289616
J Mol Endocrinol. 2012 Oct 10;49(3):165-74
pubmed: 22889684
Toxicol Sci. 2009 Sep;111(1):89-99
pubmed: 19407336
Mol Pharm. 2018 Oct 1;15(10):4361-4370
pubmed: 30114914
Environ Health Perspect. 2007 Sep;115(9):1298-305
pubmed: 17805419
Environ Int. 2019 Aug;129:343-353
pubmed: 31150976
Int Immunopharmacol. 2010 Nov;10(11):1420-7
pubmed: 20816993
Toxicol Lett. 2013 Apr 12;218(2):97-104
pubmed: 23391484
Toxicol Sci. 2021 Jul 16;182(1):82-95
pubmed: 33844015
Toxicol Sci. 2002 Jul;68(1):249-64
pubmed: 12075127
Toxicol Appl Pharmacol. 2016 Aug 1;304:18-29
pubmed: 27153767
Toxicol Appl Pharmacol. 2020 Oct 15;405:115204
pubmed: 32822737
Environ Pollut. 2019 Apr;247:1055-1063
pubmed: 30823334
Toxicology. 2013 Jun 7;308:129-37
pubmed: 23567314
Toxicol Sci. 2002 Sep;69(1):244-57
pubmed: 12215680
Aquat Toxicol. 2007 May 1;82(2):135-43
pubmed: 17374408
Liver Res. 2018 Dec;2(4):209-215
pubmed: 31245168
Arch Toxicol. 2008 Apr;82(4):239-46
pubmed: 17874065
Am J Gastroenterol. 2010 Jun;105(6):1354-63
pubmed: 20010922
Food Chem Toxicol. 2021 Jun;152:112175
pubmed: 33838175
Nat Biotechnol. 2006 Sep;24(9):1115-22
pubmed: 16964225
J Appl Toxicol. 2018 Feb;38(2):219-226
pubmed: 28857218
Toxicol In Vitro. 2020 Feb;62:104700
pubmed: 31676336
J Immunotoxicol. 2017 Dec;14(1):188-195
pubmed: 28805477
Toxicology. 2003 Feb 1;183(1-3):117-31
pubmed: 12504346
Arch Toxicol. 2017 Jun;91(6):2365-2374
pubmed: 27832320
Environ Health Perspect. 2020 Feb;128(2):27006
pubmed: 32074459
Reprod Toxicol. 2012 Jul;33(4):546-551
pubmed: 22107727
Toxicol Lett. 2009 Oct 28;190(2):163-71
pubmed: 19616083
J Biol Chem. 2015 Jun 26;290(26):16191-201
pubmed: 25934392
Environ Sci Technol. 2011 Oct 1;45(19):8037-45
pubmed: 21469664
Toxicology. 2011 Oct 9;288(1-3):8-17
pubmed: 21723365
Environ Health Perspect. 2016 Aug;124(8):1227-33
pubmed: 26978841
Chemosphere. 2014 Oct;112:225-31
pubmed: 25048910
Environ Sci Technol. 2020 Dec 15;54(24):15986-15995
pubmed: 33228354
Environ Sci Process Impacts. 2019 Nov 1;21(11):1852-1863
pubmed: 31475719
Lab Invest. 2021 Apr;101(4):490-502
pubmed: 32778734
Toxicology. 2017 Apr 1;380:23-29
pubmed: 28115241
Basic Clin Pharmacol Toxicol. 2008 Jul;103(1):1-8
pubmed: 18373647
Chem Res Toxicol. 2012 Jan 13;25(1):35-46
pubmed: 21985250
Toxicology. 2017 Mar 01;378:37-52
pubmed: 28049043
Toxicol Appl Pharmacol. 2003 Sep 1;191(2):130-46
pubmed: 12946649