The University of Queensland, Queensland Alliance for Environmental Health Sciences (QAEHS), 20 Cornwall Street, Woolloongabba, QLD 4102, Australia.
The University of Queensland, Queensland Alliance for Environmental Health Sciences (QAEHS), 20 Cornwall Street, Woolloongabba, QLD 4102, Australia.
Toxicology. 2022 Dec;482:153359. doi: 10.1016/j.tox.2022.153359. Epub 2022 Nov 2.
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 (EC). 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.
全氟和多氟烷基物质（PFAS）是无处不在的、有毒的和持久的环境化学物质，已在包括人类生物体液在内的所有环境基质中广泛检测到。尽管人类暴露于 PFAS 的复杂混合物中，但仍不确定混合物的共同暴露是否会在人类中引起遗传毒性损伤。因此，本研究在人细胞系系统中评估了 PFAS 混合物的联合遗传毒性。为了评估人类接触 PFAS 及其混合物可能造成的遗传毒性损伤，我们研究了它们在人肝癌细胞系（HepG2）中诱导细胞毒性（细胞活力）和遗传毒性（DNA 损伤）的潜力。所选的 PFAS 包括全氟壬酸（PFNA）、全氟辛烷磺酸（PFOS）、全氟癸酸（PFDA）、全氟辛酸（PFOA）和全氟己烷磺酸（PFHxS）。还使用加性指数方法确定了这些 PFAS 在二元混合物中的相互毒性。结果表明，单独和混合暴露于 PFNA、PFOS、PFDA、PFOA 和 PFHxS 会导致细胞活力呈浓度依赖性下降。加性指数值表明，PFOS+PFNA、PFOS+PFDA 和 PFOS+PFOA 的二元混合物表现出协同作用，而 PFOS+PFHxS、PFOA+PFNA、PFOA+PFDA 和 PFOA+PFHxS 的二元混合物则表现出相加作用。使用碱性彗星试验，根据各自化合物的浓度与产生 50%细胞活力抑制的有效浓度（EC）的 1/10 的浓度比（1:1），评估了 PFAS 及其混合物诱导 DNA 损伤的潜力。结果表明，单独和混合暴露于 PFNA、PFOS、PFDA、PFOA 和 PFHxS（PFOS+PFNA、PFOS+PFDA、PFOS+PFOA、PFOS+PFHxS、PFOA+PFNA、PFOA+PFDA 和 PFOA+PFHxS）会导致细胞 DNA 损伤适度增加，但未观察到剂量-反应关系。总的来说，本研究表明，在所研究的条件下，测试的 PFAS 会导致细胞活力呈浓度依赖性下降，仅导致细胞 DNA 损伤适度增加。
