关键词: 'Forever chemicals' Cytotoxicity DNA damage EMNCA Micronuclei Oxidative stress

Mesh : Animals Zebrafish Fluorocarbons / toxicity Micronucleus Tests / methods Alkanesulfonic Acids / toxicity DNA Damage / drug effects Water Pollutants, Chemical / toxicity Oxidative Stress / drug effects Erythrocytes / drug effects Reactive Oxygen Species / metabolism Mutagens / toxicity

来  源:   DOI:10.1016/j.mrgentox.2024.503788

Abstract:
Per- and polyfluoroalkyl substances (PFAS) comprise many chemicals with strong carbon-carbon and carbon-fluorine bonds and have extensive industrial applications in manufacturing several consumer products. The solid covalent bonding makes them more persistent in the environment and stays away from all types of degradation, naming them \'forever chemicals.\' Zebrafish (Danio rerio) was used to evaluate the genotoxic and cytotoxic effects of legacy PFAS, Perfluorooctane sulfonate (PFOS), and its alternatives, such as Perfluoro-2-methyl-3-oxahexanoic acid ammonium (GenX) and 7H-Perfluoro-3,6-dioxa-4-methyl-octane-1-sulfonic acid (Nafion by-product 2 [NBP2]) upon single and combined exposure at an environmental concentration of 10 µg/L for 48-h. Erythrocyte micronucleus cytome assay (EMNCA) revealed an increased frequency of micronuclei (MN) in fish erythrocytes with a significant increase in NBP2-treated fish. The order of genotoxicity noticed was NBP2 > PFOS > Mixture > GenX in D. rerio. Fish exposed to PFOS and its alternatives in single and combined experiments did not cause any significant difference in nuclear abnormalities. However, PFOS and combined exposure positively inhibit cytokinesis, resulting in an 8.16 and 7.44-fold-change increase of binucleated cells. Besides, statistically, increased levels of reactive oxygen species (ROS) and malondialdehyde (MDA) content indicate oxidative stress in D. rerio. In addition, \'forever chemicals\' resulted in cytotoxicity, as evident through changes in nucleus width to the erythrocyte length in NBP2 and mixture exposure groups. The findings revealed that PFAS alternative NBP2 is more toxic than PFOS in inducing DNA damage and cytotoxicity. In addition, all three tested \'forever chemicals\' induced ROS and lipid peroxidation after individual and combined exposure. The present work is the first to concern the genotoxicity and cytotoxicity of \'forever chemicals\' in the aquatic vertebrate D. rerio.
摘要:
全氟烷基和多氟烷基物质(PFAS)包括许多具有强的碳-碳和碳-氟键的化学品,并且在制造几种消费产品中具有广泛的工业应用。牢固的共价键使它们在环境中更持久,远离所有类型的降解,将它们命名为“永远的化学物质”。斑马鱼(Daniorerio)用于评估遗留PFAS的基因毒性和细胞毒性作用,全氟辛烷磺酸(PFOS),和它的替代品,例如全氟-2-甲基-3-氧杂己酸铵(GenX)和7H-全氟-3,6-二氧杂-4-甲基-辛烷-1-磺酸(Nafion副产物2[NBP2])在10g/L的环境浓度下单次和联合暴露48小时。红细胞微核细胞组学分析(EMNCA)显示,鱼红细胞中微核(MN)的频率增加,而经NBP2处理的鱼则显着增加。D.rerio中注意到的遗传毒性顺序为NBP2>PFOS>混合物>GenX。在单一和联合实验中,暴露于全氟辛烷磺酸及其替代品的鱼类在核异常方面没有任何显着差异。然而,全氟辛烷磺酸和联合暴露积极抑制胞质分裂,导致双核细胞增加8.16和7.44倍。此外,统计,活性氧(ROS)和丙二醛(MDA)含量的增加表明D.rerio的氧化应激。此外,“永远的化学物质”导致细胞毒性,通过NBP2和混合物暴露组的细胞核宽度到红细胞长度的变化可以明显看出。研究结果表明,PFAS替代NBP2在诱导DNA损伤和细胞毒性方面比PFOS更具毒性。此外,在单独和联合暴露后,所有三种测试的“永久化学物质”都会诱导ROS和脂质过氧化。目前的工作是第一个关注水生脊椎动物D.rerio中“永远化学物质”的遗传毒性和细胞毒性的工作。
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