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Activation of mouse and human peroxisome proliferator-activated receptor-alpha (PPARα) by perfluoroalkyl acids (PFAAs) of 5, 7, 8, 11, and 12 carbon chain lengths in C05-1 cells.
Citation:
WOLF, C. J., C. LAU, AND B. D. ABBOTT. Activation of mouse and human peroxisome proliferator-activated receptor-alpha (PPARα) by perfluoroalkyl acids (PFAAs) of 5, 7, 8, 11, and 12 carbon chain lengths in C05-1 cells. Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
This study completes our survey of the ability of PFAAs from C4 through C12 to induce PPARα activity in vitro.
Description:
PFAAs are surfactants that have been found globally in the environment and in tissues of humans and wildlife. They adversely affect perinatal survival and development in rodents and PPARα is involved in inducing these effects. Our previous study demonstrated that some PFAAs activate PPARα intransiently transfected COS-I cells.Here we test additional PFAAs for their ability to activate mouse and human PPARα. COS-I cells were transfected with either a mouse or human PPARα-responsive luciferase reporter plasmid. After 24 hours, cells were exposed to either vehicle control (0.1 % DMSO or water), PPARa agonist (WY14643, 10 uM), perfluoropentanoic acid (C5), perfluoroheptanoic acid (C7), perflourooctanoic acid (C8), perfluoroundecanoic acid (CII), or perfluorododecanoic acid (C12) at thirteen concentrations from 0.5 -100 uM. After 24 hours of exposure, cells were lysed and luciferase activity was measured. Data were analyzed using ANOVA and linear regression analysis. Relative PFAA activities were compared using C20max, the concentration at which each PFAA produces 20% of the highest response elicited by the most active PFAA for each species. C8 induced the highest activity in the human PPARα, followed by C7,C5,and Cll(C20max,4.5 uM,13 uM,45 uM and 126 uM). Cl2 had little activity (C2Omax could not be calculated). However, the highest activity in the mouse PPARα was induced by Cl2 followed by C8, Cl l, C7 and C5 (C20max, 5.4 uM, 7.2 uM, 9.2 uM, 11 uM, and 35 uM, respectively). While each PFAA activated the mouse and human PPARα, they generally induced less activity in human than in mouse PPARα. We found a pattern of increasing activity with increasing chainlength of thePFAA up to C8 withhuman PPARα, a pattern we reported previously. This study completes our survey of the ability of PFAAs from C4 through C12 to induce PPARα activity in vitro. This abstract does not necessarily reflect EPA policy.