|
|||||
|
|
An Exposure to the Oxidized DNA Enhances Both Instability of Genome and Survival in Cancer Cells |
|
| Authors: | Svetlana V Kostyuk Marina S Konkova Elizaveta S Ershova Anna J Alekseeva Tatiana D Smirnova Sergey V Stukalov Ekaterina A Kozhina Nadezda V Shilova Tatiana V Zolotukhina Zhanna G Markova Vera L Izhevskaya Ancha Baranova Natalia N Veiko |
| Institution: | 1. Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow, Russia.; 2. V.A.Negovsky’ Research Institute for General Reanimatology, Russian Academy of Medical Sciences, Moscow, Russia.; 3. Center for the Study of Chronic Metabolic Diseases, School of System Biology, George Mason University, Fairfax, Virginia, United States of America.; ENEA, Italy, |
| Abstract: | BackgroundCell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases and acts upon the cells. Response to cfDNA depends on concentrations and levels of the damage within cfDNA. Oxidized extracellular DNA acts as a stress signal and elicits an adaptive response.Principal FindingsHere we show that oxidized extracellular DNA stimulates the survival of MCF-7 tumor cells. Importantly, in cells exposed to oxidized DNA, the suppression of cell death is accompanied by an increase in the markers of genome instability. Short-term exposure to oxidized DNA results in both single- and double strand DNA breaks. Longer treatments evoke a compensatory response that leads to a decrease in the levels of chromatin fragmentations across cell populations. Exposure to oxidized DNA leads to a decrease in the activity of NRF2 and an increase in the activity of NF-kB and STAT3. A model that describes the role of oxidized DNA released from apoptotic cells in tumor biology is proposed.Conclusions/SignificanceSurvival of cells with an unstable genome may substantially augment progression of malignancy. Further studies of the effects of extracellular DNA on malignant and normal cells are warranted. |
| Keywords: | |