title: Perfluoroalkylated compounds induce cell death and formation of reactive oxygen species in cultured cerebellar granule cells.
abstract: The present communication investigates the effects of different perfluoroalkylated compounds (PFCs) on formation of reactive oxygen species (ROS) and cell death in cultured cerebellar granule cells. This allows direct comparison with similar effects found for other environmental contaminants like polychlorinated biphenyls and brominated flame-retardants. The increase in ROS formation and cell death was assayed using the fluorescent probe 2,7-dichlorofluorescin diacetate (DCFH-DA) and the trypan blue exclusion assay. The effects of the PFCs were structure dependent. Cell death was induced at relatively low concentrations by perfluorooctyl sulfonate (PFOS), perfluorooctane sulfonylamide (PFOSA) and the fluorotelomer alcohol 1H, 1H, 2H, 2H-perfluorodecanol (FTOH 8:2) with EC(50)-values of 62 ± 7.6, 13 ± 1.8 and 15 ± 4.2 μM (mean ± SD) respectively. PFOS, perfluorooctanoic acid (PFOA) and PFOSA induced a concentration dependent increase in ROS formation with EC(50)-values of 27 ± 9.0, 25 ± 11 and 57 ± 19μM respectively. Reduced cell viability and ROS formation were observed at concentration level close to what is found in serum of occupationally exposed workers. The effect of PFCs on ROS formation and cell viability was compared with other halogenated compounds and future investigations should emphasize effects of mixtures and how physical chemical properties of the compounds influence their toxicity.
authors: Norwegian Defense Research Establishment, Division for Protection and Material, P.O. Box 25, N-2027 Kjeller, Norway.
authors: Trine
authors: T
authors: Reistad
authors: Frode
authors: F
authors: Fonnum
authors: Espen
authors: E
authors: Mariussen
mesh_terms: D017738:Alkanesulfonic Acids / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D000833:Animals, Suckling; D002210:Caprylates / Q000737:chemistry / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000473:pathology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D005466:Fluorocarbons / Q000737:chemistry / Q000633:toxicity; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000633:toxicity
chemical_list: D017738:Alkanesulfonic Acids; D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D006845:Hydrocarbons, Fluorinated; D017382:Reactive Oxygen Species; D013449:Sulfonamides; C033729:fluorotelomer alcohols; C063900:perfluorooctanesulfonamide; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid