title: Perfluoroalkylated substances (PFAS) affect oxidative stress biomarkers in vitro.
abstract: Perfluoroalkylated substances (PFAS) have been widely used since 1950s and humans are exposed through food, drinking water, consumer products, dust, etc. The long-chained PFAS are persistent in the environment and accumulate in wildlife and humans. They are suspected carcinogens and a potential mode of action is through generation of oxidative stress. Seven long-chained PFAS found in human serum were investigated for the potential to generate reactive oxygen species (ROS), induce DNA damage and disturb the total antioxidant capacity (TAC). The tested PFAS were perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluoroctanoic acid (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnA), and perfluorododecanoate (PFDoA). Using the human hepatoma cell line (HepG2) and an exposure time of 24h we found that all three endpoints were affected by one or more of the compounds. PFHxS, PFOA, PFOS and PFNA showed a dose dependent increase in DNA damage in the concentration range from 2×10(-7) to 2×10(-5)M determined by the comet assay. Except for PFDoA, all the other PFAS increased ROS generation significantly. For PFHxS and PFUnA the observed ROS increases were dose-dependent. Cells exposed to PFOA were found to have a significant lower TAC compared with the solvent control, whereas a non-significant trend in TAC decrease was observed for PFOS and PFDoA and an increase tendency for PFHxS, PFNA and PFUnA. Our results indicate a possible genotoxic and cytotoxic potential of the PFAS in human liver cells.
authors.affiliation: Centre for Arctic Health & Cellular and Molecular Toxicology, Department of Public Health, Bartholins Allé 2, Aarhus University, 8000 Aarhus, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Wielsøe
authors.affiliation: Centre for Arctic Health & Cellular and Molecular Toxicology, Department of Public Health, Bartholins Allé 2, Aarhus University, 8000 Aarhus, Denmark.
authors.forename: Manhai
authors.initials: M
authors.lastname: Long
authors.affiliation: Centre for Arctic Health & Cellular and Molecular Toxicology, Department of Public Health, Bartholins Allé 2, Aarhus University, 8000 Aarhus, Denmark.
authors.forename: Mandana
authors.initials: M
authors.lastname: Ghisari
authors.affiliation: Centre for Arctic Health & Cellular and Molecular Toxicology, Department of Public Health, Bartholins Allé 2, Aarhus University, 8000 Aarhus, Denmark. Electronic address: ebj@ph.au.dk.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Bonefeld-Jørgensen
mesh_terms: D000476:Alkanesulfonates; D017738:Alkanesulfonic Acids / Q000494:pharmacology*; D000975:Antioxidants; D015415:Biomarkers; D020552:Comet Assay; D004249:DNA Damage; D005466:Fluorocarbons / Q000494:pharmacology*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species
chemical_list: D000476:Alkanesulfonates; D017738:Alkanesulfonic Acids; D000975:Antioxidants; D015415:Biomarkers; D005466:Fluorocarbons; D017382:Reactive Oxygen Species; C018959:hexadecafluoro-nonanoic acid; C076994:perfluorooctane sulfonic acid; C078626:perflexane
keywords: DNA damage; In vitro; Perfluoroalkylated substances; Reactive oxygen species; Total antioxidant capacity