Department of Environmental Science, Baylor University, Waco, TX, 76706, USA; Institute of Biomedical Studies, Baylor University, Waco, TX, 76706, USA.
Department of Environmental Science, Baylor University, Waco, TX, 76706, USA; Honors College, Baylor University, Waco, TX, 76706, USA.
Environ Pollut. 2021 Jun 15;279:116929. doi: 10.1016/j.envpol.2021.116929. Epub 2021 Mar 15.
Increasing studies are examining per- and polyfluoroalkyl substances (PFAS) induced toxicity and resulting health outcomes, including epigenetic modifications (e.g., DNA methylation, histone modification, microRNA expression). We critically reviewed current evidence from human epidemiological, in vitro, and animal studies, including mammalian and aquatic model organisms. Epidemiological studies identified the associations between perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) exposure and epigenetic changes in both adult populations and birth cohorts. For in vitro studies, various cell types including neuroblasts, preadipocytes, and hepatocytes have been employed to understand epigenetic effects of PFAS. In studies with animal models, effects of early life exposure to PFAS have been examined using rodent models, and aquatic models (e.g., zebrafish) have been more frequently used in recent years. Several studies highlighted oxidative stress as a key mediator between epigenetic modification and health effects. Collectively, previous research clearly suggest involvement of epigenetic mechanisms in PFAS induced toxicity, though these efforts have primarily focused on specific PFASs (i.e. mainly PFOS and PFOA) or endpoints (i.e. cancer). Additional studies are necessary to define specific linkages among epigenetic mechanisms and related biomarkers or phenotypical changes. In addition, future research is also needed for understudied PFAS and complex mixtures. Studies of epigenetic effects elicited by individual PFAS and mixtures are needed within an adverse outcome pathways framework, which will advance an understanding of PFAS risks to public health and the environment, and support efforts to design less hazardous chemicals.
越来越多的研究正在探讨全氟和多氟烷基物质（PFAS）引起的毒性及其导致的健康后果，包括表观遗传修饰（例如，DNA 甲基化、组蛋白修饰、microRNA 表达）。我们批判性地回顾了来自人类流行病学、体外和动物研究的现有证据，包括哺乳动物和水生模式生物。流行病学研究确定了全氟辛烷磺酸（PFOS）或全氟辛酸（PFOA）暴露与成人人群和出生队列中表观遗传变化之间的关联。对于体外研究，各种细胞类型，包括神经母细胞瘤、前脂肪细胞和肝细胞，已被用于了解 PFAS 的表观遗传效应。在动物模型研究中，使用啮齿动物模型研究了早期生活中暴露于 PFAS 的影响，近年来越来越多地使用水生模型（例如斑马鱼）。几项研究强调了氧化应激作为表观遗传修饰与健康影响之间的关键介质。总之，先前的研究清楚地表明，表观遗传机制参与了 PFAS 诱导的毒性，尽管这些研究主要集中在特定的 PFAS（即主要是 PFOS 和 PFOA）或终点（即癌症）上。需要进一步的研究来确定表观遗传机制与相关生物标志物或表型变化之间的具体联系。此外，还需要对研究较少的 PFAS 和复杂混合物进行研究。需要在不良结局途径框架内研究单个 PFAS 和混合物引起的表观遗传效应，这将有助于了解 PFAS 对公共健康和环境的风险，并支持设计危害较小的化学品的努力。
