Abstract Cell cycle alterations are among the principle hallmarks of cancer. Consequently, the study of cell cycle regulators has emerged as an important topic in cancer research, particularly in relation to environmental exposure. Particulate matter and coal dust around coal mines have the potential to induce cell cycle alterations. Therefore, in the present study, we performed chemical analyses to identify the main compounds present in two mineral coal samples from Colombian mines and performed systems chemo-biology analysis to elucidate the interactions between these chemical compounds and proteins associated with the cell cycle. Our results highlight the role of oxidative stress generated by the exposure to the residues of coal extraction, such as major inorganic oxides (MIOs), inorganic elements (IEs) and polycyclic aromatic hydrocarbons (PAH) on DNA damage and alterations in the progression of the cell cycle (blockage and/or delay), as well as structural dysfunction in several proteins. In particular, IEs such as Cr, Ni, and S and PAHs such as benzo[a]pyrene may have influential roles in the regulation of the cell cycle through DNA damage and oxidative stress. In this process, cyclins, cyclin-dependent kinases, zinc finger proteins such as TP53, and protein kinases may play a central role.

中文翻译：

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煤暴露引起的 DNA 损伤反应和细胞周期效应的系统化学生物学分析

摘要 细胞周期改变是癌症的主要标志之一。因此，细胞周期调节剂的研究已成为癌症研究中的一个重要课题，尤其是与环境暴露相关的研究。煤矿周围的颗粒物和煤尘有可能引起细胞周期的改变。因此，在本研究中，我们进行了化学分析，以确定来自哥伦比亚矿山的两个矿物煤样品中存在的主要化合物，并进行系统化学生物学分析以阐明这些化合物与与细胞周期相关的蛋白质之间的相互作用。我们的结果强调了暴露于煤炭提取残留物（如主要无机氧化物 (MIO)）所产生的氧化应激的作用，无机元素 (IE) 和多环芳烃 (PAH) 对 DNA 损伤和细胞周期进程的改变（阻塞和/或延迟）以及几种蛋白质的结构功能障碍的影响。特别是 Cr、Ni 和 S 等 IE 和苯并 [a] 芘等多环芳烃可能在通过 DNA 损伤和氧化应激调节细胞周期中发挥重要作用。在这个过程中，细胞周期蛋白、细胞周期蛋白依赖性激酶、锌指蛋白（如 TP53）和蛋白激酶可能发挥核心作用。