RESUMO
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.
RESUMO
The photoprotective effect of the methanolic extracts of three Antarctic plant species - Deschampsia antarctica Desv., Colobanthus quitensis (Kunth) Bartl., and Polytrichum juniperinum Hedw. against UV-induced DNA damage was investigated in hamster lung fibroblasts (V79 cells) and in a biomonitor organism Helix aspersas, using comet assay. The protective, mutagenic, and antimutagenic profiles of these extracts were also evaluated using haploid strains of the simple eukaryote Saccharomyces cerevisiae, and antioxidant activity were investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay, as well as the hypoxanthine/xanthine oxidase assay. At the concentration range employed, the extracts were not cytotoxic or mutagenic to S. cerevisiae. In addition, the treatment with these extracts enhanced survival, and decreased induced reverse, frameshift, and forward mutations in a dose-response manner in all UVC doses employed. The plants extracts did not generate DNA strand breaks in V79 cells, and the treatment significantly decreased DNA damage induced by UVC. Extracts significantly decreased UVC-induced lipid peroxidation in V79 cells, showing a clear antioxidant property. Moreover, results of comet assay in V79 cells, employing Fpg, Endo III, and Endo V enzymes, demonstrated significant reduction of UVC-induced DNA damage after pre-incubation with these extracts. The treatment with all tested extracts were much less efficient against UVC-induced cytotoxicity in the yeast strain defective in photolyase as compared to the wild type strain, suggesting that this DNA repair pathway is stimulated by substances present in the extracts. All extracts showed a significant inhibitory effect in the hypoxanthine/xanthine oxidase assay, and they had the ability to scavenge DPPH. In H. aspersas, the treatment was able to protect against UVC-induced damage. In conclusion, D. antarctica, C. quitensis, and P. juniperinum extracts present photoprotective properties, which can be attributed to molecules, such as flavonoids and carotenoids, which act as UV-absorbing molecules and as antioxidants, as well as stimulate DNA-repair processes.