Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Sci Total Environ. 2024 Mar 20;917:170437. doi: 10.1016/j.scitotenv.2024.170437. Epub 2024 Jan 29.
The constant exposure of humans to a mixture of low doses of toxic substances, emerging from the daily emission of toxic dust containing various metals and organic compounds in electrical and electronic waste (e-waste) recycling areas, poses potential harmful effects on health and the environment. While individually recognized as endocrine disruptors affecting hormonal balance, the combined impact of these toxic substances in a mixture remains insufficiently explored, particularly in relation to reproductive health. Thus, the aim of this in silico analysis was to: (i) assess the relationship between the exposure to a mixture of DBDE, DBDPE, TBBPA, Pb, Cd and Ni and development of male and female reproductive system disorders; and (ii) demonstrate the ability of in silico toxicogenomic tools in revealing the potential molecular mechanisms involved in the mixture toxicity. As the main data-mining tool, Comparative Toxicogenomics Database (CTD) was used, along with the ToppGene Suite portal and GeneMANIA online server. Our analysis identified 5 genes common to all the investigated substances and linked to reproductive system disorders. Notably, the most prominent interactions among these genes were physical interactions (77.64 %). Pathway enrichment analysis identified oxidative stress response as the central disrupted molecular pathway linked to reproductive pathology in the investigated mixture, while our chemical-phenotype CTD analysis uncovered additional affected pathways - apoptosis, hormonal regulation, and developmental functions. These findings highlight an increased risk of reproductive system disorders associated with the exposure to the investigated mixture of toxic substances in electronic waste recycling areas, emphasizing the urgent need for attention to address this environmental health concern. Hence, future laboratory studies should prioritize investigating the specific genes and common mechanisms identified in this study.
人类不断暴露于有毒物质的混合物中，这些有毒物质源自电子废物（e-waste）回收区域中有毒灰尘的日常排放，其中含有各种金属和有机化合物，这对健康和环境可能造成潜在的有害影响。虽然这些有毒物质已被单独确认为影响激素平衡的内分泌干扰物，但在混合物中的综合影响仍未得到充分探索，尤其是在生殖健康方面。因此，本计算机模拟分析旨在：（i）评估暴露于混合物中 DBDE、DBDPE、TBBPA、Pb、Cd 和 Ni 对男性和女性生殖系统疾病的关系；（ii）展示计算机毒理学基因组工具在揭示混合物毒性所涉及的潜在分子机制方面的能力。作为主要的数据挖掘工具，使用了比较毒理学基因组数据库（CTD），以及 ToppGene Suite 门户和 GeneMANIA 在线服务器。我们的分析确定了 5 个共同存在于所有研究物质中的基因，这些基因与生殖系统疾病有关。值得注意的是，这些基因之间最突出的相互作用是物理相互作用（77.64%）。途径富集分析确定氧化应激反应是与所研究混合物中生殖病理相关的中心破坏分子途径，而我们的化学表型 CTD 分析揭示了其他受影响的途径——细胞凋亡、激素调节和发育功能。这些发现强调了与电子废物回收区域中所研究的有毒物质混合物暴露相关的生殖系统疾病风险增加，强调迫切需要关注解决这一环境健康问题。因此，未来的实验室研究应优先调查本研究中确定的特定基因和共同机制。
