Genotoxicity assessment of per- and polyfluoroalkyl substances mixtures in human liver cells (HepG2)

全氟辛酸 遗传毒性 全氟辛烷 化学 DNA损伤 环境化学 彗星试验 活力测定 EC50型 生物监测 毒性 生物化学 细胞 体外 DNA 有机化学 磺酸盐
作者
Atinuke F. Ojo,Cheng Peng,J. C. Ng
出处
期刊:Toxicology [Elsevier BV]
卷期号:482: 153359-153359 被引量:11
标识
DOI:10.1016/j.tox.2022.153359
摘要

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, toxic, and persistent environmental chemicals of concern that have been widely detected in all environmental matrices including human biological fluids. Although humans are exposed to complex mixtures of PFAS, it remains uncertain whether the co-exposure to PFAS mixtures could induce genotoxic damage in humans. Hence, this study evaluated the combined genotoxicity of PFAS mixtures in a human cell line system. To assess the possible genotoxic damage caused by human exposure to PFAS and their mixtures, we investigated their potential to induce cytotoxicity (cell viability) and genotoxicity (DNA damage) in a human liver cell line (HepG2). The selected PFAS include perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS). The interaction toxicities of these PFAS in binary mixtures were also determined using the additive index approach. The results revealed that exposure to PFNA, PFOS, PFDA, PFOA, and PFHxS singly and in binary mixtures induced a concentration-dependent decrease in cell viability. The additive index values indicated that the binary mixtures of PFOS + PFNA, PFOS + PFDA, and PFOS + PFOA displayed synergistic interaction, whereas the binary mixtures of PFOS + PFHxS, PFOA + PFNA, PFOA + PFDA, and PFOA + PFHxS behaved additively. Using the alkaline Comet assay, the potential of PFAS and their mixtures to induce DNA damage was evaluated based on a 1:1 ratio of the concentration of respective compounds required to produce a 1/10th of effective concentrations causing 50 % inhibition in cell viability (EC50). The results revealed that exposure to PFNA, PFOS, PFDA, PFOA, and PFHxS singly and in binary mixtures (PFOS + PFNA, PFOS + PFDA, PFOS + PFOA, PFOS + PFHxS, PFOA + PFNA, PFOA + PFDA, and PFOA + PFHxS) caused a moderate increase in cellular DNA damage, but no dose-response relationship was observed. Overall, this study indicates that the tested PFAS causes a concentration-dependent decrease in cell viability and only a modest increase in cellular DNA damage under these conditions.
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