Abstract：
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.
摘要：
草甘膦,世界上使用最广泛的除草剂，尽管有大量证据表明对健康产生不利影响，但仍具有低毒性等级。此外，基于草甘膦的配方（GBF）含有几种其他化学物质，其中一些已知是有害的。此外,慢性，农村工人急性接触GBF可能导致健康损害，如神经退行性疾病和癌症。P53被称为肿瘤抑制蛋白，作为细胞对应激和DNA损伤反应的关键调节剂。因此,TP53基因突变，编码p53，是在各种类型的癌症中发现的常见遗传改变。因此,这项研究旨在评估GBF在两种胶质母细胞瘤细胞系中的细胞毒性和遗传毒性：U87MG（TP53-properent）和U251MG（TP53-突变体）。此外,该研究旨在使用系统生物学在一个含有p53的网络和另一个没有p53的网络中鉴定与GBF暴露反应有关的主要蛋白。MTT法用于研究GBF在细胞系中的毒性，克隆形成试验用于研究细胞存活，彗星试验用于遗传毒性评价。对于数据分析，应用了生物信息学工具，如String12.0和Stitch5.0，作为在Cytoscape3.10.1程序中设计二进制网络的基础。从体外测试分析来看，在从10ppm开始的剂量下观察到细胞活力降低。U251MG和U87MG细胞系浓度为10ppm和30ppm的彗星试验，分别观察DNA损伤。系统生物学产生的网络表明，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很重要。在TP53突变网络中未出现的过程。
