Genotoxicity and cytotoxicity assessment of 'forever chemicals' in zebrafish (Danio rerio)

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2024-07-01 DOI:10.1016/j.mrgentox.2024.503788

Shaloo Singh , Krishna Gautam , Snober S. Mir , Sadasivam Anbumani

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引用次数: 0

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.

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斑马鱼（Danio rerio）体内 "永久化学品 "的遗传毒性和细胞毒性评估

全氟烷基和多氟烷基物质（PFAS）由许多具有强碳-碳键和碳-氟键的化学物质组成，在一些消费品的制造中有着广泛的工业应用。牢固的共价键使它们在环境中更加持久，并且不会被各种类型的降解，因此被命名为 "永恒的化学物质"。斑马鱼（Danio rerio）被用来评估传统全氟辛烷磺酸（PFOS）及其替代品（如全氟-2-甲基-3-氧杂己酸铵（GenX）和 7H-全氟-3、6-dioxa-4-methyl-octane-1-sulfonic acid (Nafion 副产品 2 [NBP2])。红细胞微核细胞组测定（EMNCA）显示，鱼类红细胞中的微核（MN）频率增加，NBP2 处理的鱼类微核频率显著增加。在 D. rerio 中，注意到的遗传毒性顺序为 NBP2 > PFOS > Mixture > GenX。鱼类在单一和组合实验中接触全氟辛烷磺酸及其替代品不会导致核异常的显著差异。但是，接触全氟辛烷磺酸及其替代品会抑制细胞分裂，导致双核细胞分别增加了 8.16 倍和 7.44 倍。此外，据统计，活性氧（ROS）和丙二醛（MDA）含量的增加表明 D. rerio 中存在氧化应激。此外，"永远的化学品 "会导致细胞毒性，这在 NBP2 和混合物暴露组的细胞核宽度与红细胞长度的变化中显而易见。研究结果表明，在诱导 DNA 损伤和细胞毒性方面，全氟辛烷磺酸替代物 NBP2 的毒性高于全氟辛烷磺酸。此外，所有三种受测 "永久化学品 "在单独接触和混合接触后都会诱发 ROS 和脂质过氧化反应。本研究首次涉及 "永久化学品 "在水生脊椎动物 D. rerio 中的遗传毒性和细胞毒性。

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来源期刊

Mutation research. Genetic toxicology and environmental mutagenesis 生物-毒理学

CiteScore

3.80

自引率

5.30%

发文量

审稿时长

105 days

期刊介绍： Mutation Research - Genetic Toxicology and Environmental Mutagenesis (MRGTEM) publishes papers advancing knowledge in the field of genetic toxicology. Papers are welcomed in the following areas: New developments in genotoxicity testing of chemical agents (e.g. improvements in methodology of assay systems and interpretation of results). Alternatives to and refinement of the use of animals in genotoxicity testing. Nano-genotoxicology, the study of genotoxicity hazards and risks related to novel man-made nanomaterials. Studies of epigenetic changes in relation to genotoxic effects. The use of structure-activity relationships in predicting genotoxic effects. The isolation and chemical characterization of novel environmental mutagens. The measurement of genotoxic effects in human populations, when accompanied by quantitative measurements of environmental or occupational exposures. The application of novel technologies for assessing the hazard and risks associated with genotoxic substances (e.g. OMICS or other high-throughput approaches to genotoxicity testing). MRGTEM is now accepting submissions for a new section of the journal: Current Topics in Genotoxicity Testing, that will be dedicated to the discussion of current issues relating to design, interpretation and strategic use of genotoxicity tests. This section is envisaged to include discussions relating to the development of new international testing guidelines, but also to wider topics in the field. The evaluation of contrasting or opposing viewpoints is welcomed as long as the presentation is in accordance with the journal''s aims, scope, and policies.