Epigenetic toxicity of PFOA in HepG2 cells and its role in lipid metabolism

PFOA;HepG2;epigenetics;DNA-methylation;lipid metabolism

Wen, Yi ; Irudayaraj ; Joseph MK

关键词: PFOA;    HepG2;    epigenetics;    DNA-methylation;    lipid metabolism;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/105717/WEN-THESIS-2019.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Perfluorooctanoic acid (PFOA), a man-made stable perfluoroalkyl acid is used widely in the process of synthesizing fluoropolymers for the manufacturing of various daily products such as Teflon. PFOA is extremely persistent in the environment and can be detected in many organisms including humans. Different studies have shown the potential of PFOA causing diseases in animals. Previous study has suggested PFOA-induced hepatocellular damage over time with unusual fat deposit and liver enlargement. To closely study the underlying mechanisms of PFOA induced hepatocellular damage. Liver hepatocellular carcinoma cell line HepG2 was used as a model to study the PFOA induced inflammation in vitro on the cellular, epigenetic and metabolic levels. HepG2 cells were treated with 20 μM, 100 μM, 200 μM, 400 μM PFOA dissolved in DMSO for 48 hours before harvested for DNA, RNA and assays. The mRNA expression levels of cell cycle and proliferation genes are affected significantly, as well as the mRNA expression levels of TETs. Due to the unusual fat deposits in PFOA treated animals observed in prior studies, essential lipid metabolism gene were also studied and of which the mRNA expression levels are also changed, especially those regarding beta-oxidation pathway and lipid synthesis. Global methylation level of HepG2 cells was found to be in overall inverse proportion with different dosages of PFOA and had corresponding trends with mRNA expression of most genes of interest. Lipid quantification has also showed PFOA dose-dependent increase in the lipid accumulation in HepG2 cells. These evidences showed PFOA induced epigenetic changes play a major role in lipid metabolism genes activation and modulation in lipid metabolism, potentially causes abnormal fat deposit, liver inflammation and carcinogenesis.