草甘膦是世界上使用最广泛的除草剂，尽管有大量证据表明对健康有不利影响，但其毒性等级较低。此外，基于草甘膦的制剂 (GBF) 还含有其他几种化学物质，其中一些已知是有害的。此外，农村工人长期和急性接触 GBF 可能会导致健康损害，例如神经退行性疾病和癌症。 P53 被称为肿瘤抑制蛋白，是细胞对压力和 DNA 损伤反应的关键调节因子。因此，编码 p53 的 TP53 基因突变是各种癌症中常见的基因改变。因此，本研究旨在评估 GBF 在两种胶质母细胞瘤细胞系：U87MG（TP53 熟练）和 U251MG（TP53 突变）中的细胞毒性和基因毒性。此外，该研究旨在使用系统生物学在包含 p53 的网络和另一个不含 p53 的网络中识别参与 GBF 暴露反应的主要蛋白质。 MTT法用于研究GBF对细胞系的毒性，克隆形成法用于研究细胞存活，彗星法用于遗传毒性评价。在数据分析方面，应用了String 12.0和Stitch 5.0等生物信息学工具，作为Cytoscape 3.10.1程序中设计二进制网络的基础。根据体外测试分析，从 10ppm 开始的剂量观察到细胞活力下降。 Comet Assay在10ppm和30ppm浓度下分别对U251MG和U87MG细胞系观察到DNA损伤。系统生物学生成的网络表明，p53 的存在对于调节涉及遗传稳定性和神经毒性的生物过程非常重要，而 TP53 突变体网络中没有出现这些过程。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Glyphosate, the world's most widely used herbicide, has a low toxicity rating despite substantial evidence of adverse health effects. Furthermore, glyphosate-based formulations (GBFs) contain several other chemicals, some of which are known to be harmful. Additionally, chronic, and acute exposure to GBFs among rural workers may lead to health impairments, such as neurodegenerative diseases and cancer. P53 is known as a tumor suppressor protein, acting as a key regulator of the cellular response to stress and DNA damage. Therefore, mutations in the TP53 gene, which encodes p53, are common genetic alterations found in various types of cancer. Therefore, this study aimed to evaluate the cytotoxicity and genotoxicity of GBF in two glioblastoma cell lines: U87MG (TP53-proficient) and U251MG (TP53-mutant). Additionally, the study aimed to identify the main proteins involved in the response to GBF exposure using Systems Biology in a network containing p53 and another network without p53. The MTT assay was used to study the toxicity of GBF in the cell lines, the clonogenic assay was used to investigate cell survival, and the Comet Assay was used for genotoxicity evaluation. For data analysis, bioinformatics tools such as String 12.0 and Stitch 5.0 were applied, serving as a basis for designing binary networks in the Cytoscape 3.10.1 program. From the in vitro test analyses, it was observed a decrease in cell viability at doses starting from 10 ppm. Comet Assay at concentrations of 10 ppm and 30 ppm for the U251MG and U87MG cell lines, respectively observed DNA damage. The network generated with systems biology showed that the presence of p53 is important for the regulation of biological processes involved in genetic stability and neurotoxicity, processes that did not appear in the TP53-mutant network.Copyright © 2024 Elsevier B.V. All rights reserved.