Torres-Ávila Jose F, Espitia-Pérez Lyda, Bonatto Diego, Silva Fernanda Rabaioli da, Oliveira Iuri Marques de, Silva Luís F O, Corrêa Dione Silva, Dias Johnny Ferraz, Silva Juliana da, Henriques João Antonio Pêgas
Universidade Federal do Rio Grande do Sul, Centro de Biotecnologia, Departamento de Biofísica, Porto Alegre, RS, Brazil.
Universidad Simón Bolívar, Facultad de Ciencias Básicas y Biomédicas, Barranquilla, Colombia.
Genet Mol Biol. 2020 Jun 26;43(3):e20190134. doi: 10.1590/1678-4685-GMB-2019-0134. eCollection 2020.
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.
细胞周期改变是癌症的主要标志之一。因此,细胞周期调节因子的研究已成为癌症研究中的一个重要课题,特别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诱导细胞周期改变。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煤矿的两个矿物煤样品中存在的主要化合物,并进行了系统化学生物学分析,以阐明这些化合物与细胞周期相关蛋白之间的相互作用。我们的结果突出了接触煤炭开采残留物(如主要无机氧化物(MIOs)、无机元素(IEs)和多环芳烃(PAH))所产生的氧化应激对DNA损伤、细胞周期进程改变(阻滞和/或延迟)以及几种蛋白质结构功能障碍的作用。特别是,诸如铬、镍和硫等无机元素以及诸如苯并[a]芘等多环芳烃可能通过DNA损伤和氧化应激在细胞周期调节中发挥重要作用。在此过程中,细胞周期蛋白、细胞周期蛋白依赖性激酶、诸如TP53等锌指蛋白以及蛋白激酶可能发挥核心作用。