有毒金属(镉(Cd),铅(Pb),汞(Hg)和砷(As))和增塑剂(邻苯二甲酸二(2-乙基己基)酯(DEHP),邻苯二甲酸二丁酯(DBP))和双酚A(BPA))已被建议有助于大肠癌(CRC)的发展。萝卜硫素(SFN),来自十字花科蔬菜的异硫氰酸盐,减少化学致癌易感性,但已被证明是一个朋友或敌人,这取决于各种因素。通过进行机械毒理学数据挖掘方法,这项研究旨在确定SFN是否可以在基因水平上减轻有毒金属和/或邻苯二甲酸盐/BPA混合物诱导的CRC。比较毒性基因组学数据库,ToppGeneSuite门户,Cytoscape软件,使用InteractVenn和基因表达综合(GEO)数据库(GEO2R工具)。在所有被研究物质的相互基因中,SFN仅通过PTGS2产生保护性影响。其他建议的保护SFN目标包括ABCA1,ALDH2,BMP2,DPYD,MYC,SLCO2A1和SOD2,仅在邻苯二甲酸酯/BPA暴露的情况下。与针对有毒金属混合物诱导的CRC的SFN保护相关的唯一额外基因是ABCB1。此外,提取的前15个分子途径中的大多数用于研究SFN对邻苯二甲酸盐和BPA混合相关CRC发展的影响与癌症发展直接相关,有毒金属混合物的情况并非如此。目前的研究表明,与有毒金属混合物相比,SFN是一种更有效的针对邻苯二甲酸酯/BPA混合物诱导的CRC的化学保护剂。它还提出了计算方法作为指导进一步研究的简单工具的价值,选择合适的生物标志物并探索毒性机制。
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.