- Yu F. Sasaki (Laboratory of Genotoxicity, Faculty of Chemical and Biological Engineering, Hachinohe National College of Technology / Department of Pharmaceutical Health Care Faculty of Pharmaceutical Sciences, Himeji Dokkyo University / firstname.lastname@example.org)
1) BOZO Research Center Inc. , 2) Laboratory of Genotoxicity, Faculty of Chemical and Biological Engineering, Hachinohe National College of Technology , 3) Iwate Institute of Environ Health Sci. , 4) Department of Pharmaceutical Health Care Faculty of Pharmaceutical Sciences, Himeji Dokkyo University , 5) Graduated School of Grobal Environmental Studies, Kyoto University , 6) Agilent Technologies Japan Ltd.
Perfluoroalkyl acids (PFAAs) have been widely used since 1950s. The long chained-PFAAs, such as perfluorooctanoic acid (PFOA) are persistent and bio-accumulative, and are detected in humans. PFOA, which is a peroxisome proliferator activated receptor (PPAR) α agonist, has been suggested to be a carcinogen in epidemiological and animal studies. In some studies PFOA is shown to be non-mutagenic in Ames and micronucleus tests, but in other studies it caused oxidative DNA damage and micronucleus formation. However, there has been no report that has examined whether PFOA-induced genotoxicity is mediated by PPARα. In order to relate genotoxicity of PFAAs to PPARα, we conducted two kinds of comet assays (cellular and acellular), a micronucleus (MN) test, and a TK mutation assay with and without PPARαantagonists by using human lymphoblastoid cells. PFAAs at 125-1000 μg/mL showed positive responses in the cellular comet assay but not in the MN test and TK mutation assay. A PPARα antagonist GW6471 (2 μg/mL) only partly reduced PFOA-induced DNA damage (in the cellular comet assay), but abolished PFOA-induced intracellular ROS formation. PFAAs with 8-12 carbons also showed positive responses in the acellular comet assay where there is no cellular function such as PPAR. Therefore, PFOA-induced DNA damage was partly related to the oxidative stress via PPARα, without manifestation of chromosome aberration and point mutation in this cell line.