Genotoxic risk and oxidative DNA damage in HepG2 cells exposed to perfluorooctanoic acid.
Perfluorooctanoic acid (C8HF15O2, PFOA) is widely used in various industrial fields for decades and it is environmentally bioaccumulative. PFOA is known as a potent hepatocarcinogen in rodents. But it is not yet clear whether it is also carcinogenic in humans, and the genotoxic effects of PFOA on human cells have not yet been examined. In this study, the genotoxic potential of PFOA was investigated in human hepatoma HepG2 cells in culture using single cell gel electrophoresis (SCGE) assay and micronucleus (MN) assay. In order to clarify the underlying mechanism(s) we measured the intracellular generation of reactive oxygen species (ROS) using dichlorofluorescein diacetate as a fluorochrome. The level of oxidative DNA damage was evaluated by immunocytochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG) in PFOA-treated HepG2 cells. PFOA at 50-400 microM caused DNA strand breaks and at 100-400 microM MN in HepG2 cells both in a dose-dependent manner. Significantly increased levels of ROS and 8-OHdG were observed in these cells. We conclude that PFOA exerts genotoxic effects on HepG2 cells, probably through oxidative DNA damage induced by intracellular ROS.
Yao
Xiaofeng
X
Department of Toxicology, Dalian Medical University, 465 Zhongshan Road, Dalian, 116027 Liaoning, China.
Zhong
Laifu
L
D002210:Caprylates / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D020552:Comet Assay; D004249:DNA Damage; D005466:Fluorocarbons / Q000633:toxicity*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D018570:Risk Assessment; D014407:Tumor Cells, Cultured
D002210:Caprylates; D005466:Fluorocarbons; D017382:Reactive Oxygen Species; C023036:perfluorooctanoic acid