有毒金属（镉（Cd），铅（Pb），汞（Hg）和砷（As））和可塑剂（双（2 - 乙基己基）邻苯二甲酸酯（DEHP），二丁基邻苯二甲酸酯（DBP））和双酚A（BPA））被认为有助于结直肠癌（CRC）的进展。芥子硫醇（SFN）是十字花科蔬菜中的异硫氰酸盐，可以减少化学致癌性的易感性，但根据不同的因素表现为朋友还是敌人。通过进行机械毒理基因组数据挖掘方法，本研究旨在确定SFN是否可以在基因水平上减轻有毒金属和/或邻苯二甲酸酯/BPA混合物诱导的CRC。使用了比较毒理基因组数据库，ToppGene Suite门户网站，Cytoscape软件，InteractiVenn和基因表达数据库（GEO）（GEO2R工具）。在所有调查物质的共有基因中，仅通过PTGS2，SFN才有保护作用。其他提出的具有保护作用的SFN靶标包括ABCA1，ALDH2，BMP2，DPYD，MYC，SLCO2A1和SOD2，仅在邻苯二甲酸酯/BPA暴露的情况下。仅仅附加的基因与邻苯二甲酸酯/BPA混合诱导的有毒金属混合型CRC的SFN保护相关，为ABCB1。此外，从与癌症发展直接相关的15个最重要的分子途径中提取出来的SFN对邻苯二甲酸酯和BPA混合物相关的CRC发展的影响，大多数是直接与癌症发展相关的，而这并不是有毒金属混合物的情况。当前研究表明，SFN是一种更有效的化学防护剂，可以防止邻苯二甲酸酯/BPA混合物诱导的CRC，而不是有毒金属混合物。它还表明了计算方法作为指导进一步研究，选择适当的生物标志物和探索毒性机制的简单工具的价值。Copyright © 2023. Elsevier Inc. 发布。

Toxic metals (cadmium (Cd), lead (Pb), mercury (Hg) and arsenic (As)) and plastificators (bis (2 - ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP)) and bisphenol A (BPA)) have been suggested to aid in colorectal carcinoma (CRC) advancement. Sulforaphane (SFN), isothiocyanate from cruciferous vegetables, diminishes chemical carcinogenesis susceptibility, but has been shown to act as a friend or a foe depending on various factors. By conducting the mechanistic toxicogenomic data mining approach, this research aimed to determine if SFN can alleviate toxic-metal and/or phthalate/BPA mixture-induced CRC at the gene level. Comparative Toxicogenomics Database, ToppGene Suite portal, Cytoscape software, InteractiVenn and Gene Expression Omnibus (GEO) database (GEO2R tool) was used. Among the mutual genes for all the investigated substances, SFN had a protective impact only through PTGS2. Other proposed protective SFN-targets included ABCA1, ALDH2, BMP2, DPYD, MYC, SLCO2A1, and SOD2, only in the case of phthalates/BPA exposure. The only additional gene relevant for SFN protection against the toxic metal mixture-induced CRC was ABCB1. Additionally, the majority of the top 15 molecular pathways extracted for SFN impact on phthalate and BPA mixture-linked CRC development were directly linked with cancer development, which was not the case with the toxic metal mixture. The current research has indicated that SFN is a more effective chemoprotective agent against CRC induced by phthalates/BPA mixture than by toxic-metal mixture. It has also presented the value of computational methods as a simple tool for directing further research, selecting appropriate biomarkers and exploring the mechanisms of toxicity.Copyright © 2023. Published by Elsevier Inc.