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对葱属植物细胞的苯氧羧酸类除草剂派草丹的遗传毒性和细胞毒性及其分子对接研究以揭示遗传毒性机制。

Genotoxic and cytotoxic effects of pethoxamid herbicide on Allium cepa cells and its molecular docking studies to unravel genotoxicity mechanism.

机构信息

Molecular Biology and Genetics Department, Faculty of Arts and Sciences, Uşak University, 1 Eylül Campus, 64300, Usak, Turkey.

Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan.

出版信息

Environ Sci Pollut Res Int. 2022 Sep;29(42):63127-63140. doi: 10.1007/s11356-022-20166-5. Epub 2022 Apr 22.

DOI:10.1007/s11356-022-20166-5
PMID:35449332
Abstract

Pethoxamid is chloroacetamide herbicide. Pethoxamid is commonly used to kill different weeds in various crops. Pethoxamid can leach in the water and soil and can cause toxic effects to other non-target species. Current study is therefore aimed to perform the investigation of the cytotoxic and genotoxic effects of pethoxamid on Allium cepa cells.The root growth, mitotic index (MI), chromosomal aberrations (CAs), and DNA damage were assessed through root growth inhibition, A. cepa ana-telophase, and alkaline comet assays, respectively. Furthermore, molecular docking was performed to evaluate binding affinity of pethoxamid on DNA and very-long-chain fatty acid (VLCFA) synthases. In root growth inhibition test, onion root length was statistically significantly decreased in a concentration dependent manner. Concentration- and time-dependent decreases in MI were observed, whereas increase in CAs such as disturbed ana-telophase, chromosome laggards, stickiness, anaphase bridges, and DNA damage was caused by the pethoxamid on A. cepa root cells. Molecular docking revealed that pethoxamid binds selectively to GC-rich regions in the minor groove of the DNA structure and showed remarkable binding affinity against all synthases taking part in the sequential biosynthesis of VLCFAs. It was concluded that the pethoxamid-induced genotoxicity and cytotoxicity may be through multiple binding ability of this herbicide with DNA and VLCFA synthases.

摘要

苯氧草酰胺是一种氯乙酰胺类除草剂。苯氧草酰胺常用于杀死各种作物中的不同杂草。苯氧草酰胺会在水中和土壤中渗透,并对其他非目标物种造成有毒影响。因此,目前的研究旨在研究苯氧草酰胺对洋葱细胞的细胞毒性和遗传毒性作用。通过根生长抑制、洋葱根尖细胞有丝分裂末期和碱性彗星试验,分别评估了苯氧草酰胺对根生长、有丝分裂指数(MI)、染色体畸变(CAs)和 DNA 损伤的影响。此外,还进行了分子对接,以评估苯氧草酰胺与 DNA 和非常长链脂肪酸(VLCFA)合成酶的结合亲和力。在根生长抑制试验中,洋葱根长在浓度依赖性的方式下呈统计学显著下降。观察到 MI 呈浓度和时间依赖性下降,而苯氧草酰胺引起的 CAs 增加,如紊乱的有丝分裂末期、染色体滞后、粘性、后期桥、和 DNA 损伤。分子对接表明,苯氧草酰胺选择性地结合到 DNA 结构的小沟中富含 GC 的区域,并显示出对参与 VLCFA 顺序生物合成的所有合成酶的显著结合亲和力。结论是,苯氧草酰胺引起的遗传毒性和细胞毒性可能是通过该除草剂与 DNA 和 VLCFA 合成酶的多种结合能力。

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