Cell cycle perturbations induced by Cisplatin in normal and tumor transformed cells

0142179 - FGU-C 20010233 RIV CZ eng J - Článek v odborném periodiku
Mareš, Vladislav - Mazzini, G. - Lisá, Věra - Ferrari, C. - Malík, Radek - Šedo, A.
Cell cycle perturbations induced by Cisplatin in normal and tumor transformed cells.
Acta Universitatis Purkynianae. Studia biologica. Roč. 5, - (2001), s. 23-29. ISSN 1212-3137
Grant ostatní: GA UK(XC) 58/1999/C; LF UK(XC) 206019-2-"Oncology"
Výzkumný záměr: CEZ:AV0Z5011922
Klíčová slova: cell cycle * cisplatin * DNA content
Kód oboru RIV: FD - Onkologie a hematologie

Cisplatin (cis-dichlorodiamineplatinum II) is a cytostatic used for treatment of tumors, including those of the brain. Molecular mechanisms of cell cycle effect of this drug are not entirely understood. In this study we compared the cell cycle changes induced by Cisplatin in tumor transformed rat C6 glioma cells and normal dividing rat brain cells, as represented by glial cells in cultures and germinative cells of the immature cerebellum exposed to the drug in situ. In normal cells, we found an early and profound alerting of the G1-phase checking point while changes in G2/M-phase compartment were much lower and found only in the cells exposed to Cisplatin in situ. In tumor transformed C6 glioma cells the G2/M checking point was found to be main, and/or, the only mechanism responding to Cisplatin. In addition, the number of G2/M blocked cells in C6 glioma cultures was remarkably increasing with time which indicates great intrapopulation heterogeneity in the efficiency of cell cycle control in these cells or their uneven sensitivity to Cisplatin. The cells inhibited in cycling in G2/M deserves further analysis as to the duration of this effect, effectiveness of the post-synthetic DNA repair and recruitment of cells to apoptosis. In normal populations, possibilities of their escape the G1 checking point due to some specifities of Cisplatin molecular action (e.g. suppressing some genome damage- signaling mechanisms) or a differential affection of the intracellular targets of the drug, especially of the mitochondria and the nuclei, seem also to be worth of analyzing.
Trvalý link: http://hdl.handle.net/11104/0039887