Perfluoroalkylated substances (PFAS) affect oxidative stress biomarkers in vitro

• Effect on oxidative stress factors of seven long-chained PFAS was investigated.
• The selected PFAS were: PFHxS, PFOS, PFOA, PFNA, PFDA, PFUnA and PFDoA.
• Four of the PFAS showed dose-dependent increase in DNA damage.
• Six PFAS increased ROS generation and the increase were dose-dependent for 2 PFAS.
• PFOA significantly decreased the total antioxidant capacity.

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 24 h 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.