Department of Toxicology "Akademik Danilo Soldatović", Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Department of Toxicology "Akademik Danilo Soldatović", Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Sci Total Environ. 2024 Nov 1;949:175187. doi: 10.1016/j.scitotenv.2024.175187. Epub 2024 Jul 31.
Pesticides are crucial for crop protection and have seen a 50 % increase in use in the last decade. Besides preventing significant crop losses their use has raised health concerns due to consumer exposure through residues in food and water. The toxicity data from individual components is often used to assess overall mixture toxicity, but uncertainty persists in understanding the behaviors of individual chemicals within these mixtures. Assessing the risk of pesticide mixture exposure remains challenging, potentially leading to overestimation or underestimation of toxicity. This study aims to establish a possible link between exposure to a herbicide mixture and genotoxic effects, focusing on cancer development. Our analysis was focused on four herbicides glyphosate, nicosulfuron, S-metolachlor and terbuthylazine. To determine the link between genes associated with cancer development due to exposure to herbicide mixture, a CTD database tools were used. Through the ToppFun tool molecular function and biological process associated with genes common to the disease of interest and selected herbicides were evaluated. And finally, GeneMANIA was used in order to analyze the function and interaction between common genes of herbicide mixture. Among the 7 common genes for herbicide mixture and cancer development coexpression characteristics were dominant at 65.41 %, 22.14 % of annotated genes shared the same pathway and 7.88 % showed co-localization. Among six target genes involved in genetic disease development co-expression was dominant at 87.34 %, colocalization at 8.03 % and shared protein domains at 4.52 %. Comprehensive molecular analyses, encompassing genomics, proteomics, and pathway analysis, are essential to unravel the specific mechanisms involved in the context of the studied mixture and its potential carcinogenic effects.
农药对作物保护至关重要,在过去十年中使用量增加了 50%。除了防止作物大量减产外,由于消费者通过食物和水中的残留接触到农药,其使用也引起了健康问题。通常使用个别成分的毒性数据来评估混合物的整体毒性,但对于这些混合物中个别化学物质的行为仍存在不确定性。评估农药混合物暴露的风险仍然具有挑战性,可能导致毒性的高估或低估。本研究旨在确定接触除草剂混合物与遗传毒性效应之间的可能联系,重点是癌症的发展。我们的分析集中在四种除草剂草甘膦、烟嘧磺隆、S-异丙甲草胺和特丁津上。为了确定由于暴露于除草剂混合物而与癌症发展相关的基因之间的联系,使用了 CTD 数据库工具。通过 ToppFun 工具,评估了与感兴趣疾病和选定除草剂相关的基因的分子功能和生物学过程。最后,使用 GeneMANIA 分析除草剂混合物共同基因之间的功能和相互作用。在与除草剂混合物和癌症发展相关的 7 个共同基因中,共表达特征占主导地位,为 65.41%,22.14%的注释基因具有相同的途径,7.88%显示共定位。在涉及遗传疾病发展的六个靶基因中,共表达占主导地位,为 87.34%,共定位为 8.03%,共享蛋白结构域为 4.52%。综合的分子分析,包括基因组学、蛋白质组学和途径分析,对于揭示所研究混合物及其潜在致癌作用的具体机制至关重要。