Epigenetic Modifications, and Alterations in Cell Cycle and Apoptosis Pathway in A549 Lung Carcinoma Cell Line upon Exposure to Perfluoroalkyl Substances

Abstract

Per- and polyfluoroalkyl substances (PFAS) are a group of human-made compounds with strong C-F bonds, and have been used in various manufacturing industries for decades. PFAS have been reported to deleterious effect on human health, which has led to studies identifying the possible toxicity and toxicity routes of these compounds. We report that these compounds have the potential to cause epigenetic modifications, and to induce dysregulation in the cell proliferation cycle as well as apoptosis in A549 lung cancer cells when exposed to 10-, 200- and 400 μM concentrations of each compound. Our studies show that exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) may cause hypomethylation in the epigenome, but changes in the epigenetic makeup are not evident upon exposure to GenX. We establish that exposure to lower doses of these compounds causes the cells’ balance to shift to cell proliferation, whereas exposure to higher concentrations shifts the balance more towards apoptosis. Furthermore, the apoptosis pathway upon exposure to GenX, PFOA, and PFOS has also been identified. Our findings suggest that exposure to any of these compounds may have profound effects in patients with pre-existing lung conditions or could trigger lung cancinogenesis.