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Biologists have studied the way death of cells with damaged DNA

Employees of the Faculty of Fundamental Medicine of Moscow State University named after MV Lomonosov investigated the effect of genotoxic stress on the stability of the genome, as well as various methods of eliminating defective cells. This condition occurs due to a variety of DNA damage and can lead to cell death. This work was supported by the Russian Science Foundation, and the article was published in the prestigious scientific journal Oncogene. Research will help improve cancer treatments.

Ensuring the stability of the genome is necessary for the normal functioning of the cell. Errors in the replication (doubling) of DNA, as well as a variety of external factors: ultraviolet radiation, chemicals, etc., can violate this stability. The very structure of the hereditary material changes in this case – this is called genotoxic stress. It is fraught with the development of cancer and other dangerous diseases.

There are special cellular mechanisms aimed at restoring the initial state of DNA. However, in the event of the accumulation of an excessively large number of genetic lesions, which for one reason or another could not be eliminated, the programmed process of the death of such cells is activated. This is a necessary measure to eliminate defective hereditary material. Among the various scenarios caused by DNA damage, apoptosis is the most studied. In this case, the cell breaks up into apoptotic bodies, which are absorbed either by its neighbors or by “professional eaters” of macrophages. As a result, the contents of the cell do not spill into the surrounding tissues, and its aggressive components do not cause cell destruction and inflammatory reactions.

In recent years, scientists have described various non-apoptotic methods of death, such as pathological necrosis. In this case, the cell gradually swells, and its membrane is destroyed. During this process, the environment is also damaged. Regulated necrosis is called necroptosis. Autophagy — the digestion of non-functional or defective components — also belongs to a number of the most well-known non-apoptotic mechanisms. It can both kill a cell, and in certain situations make it resistant to various influences.

“In this study, young laboratory employees Yevgeny Prokhorova, Alexander Egorshin and Gelin Kopein showed that non-apoptotic forms of cell death are also activated after genotoxic stress. Along with the adaptive reactions that accompany them, they can play a decisive role in antitumor therapy, ”says project manager Boris Zhivotovsky, professor, head of the laboratory for the study of apoptosis mechanisms, faculty of fundamental medicine, Moscow State University named after MV Lomonosov.

Scientists conducted a voluminous work, during which they analyzed many different ways of killing cells with damaged DNA. The authors collected the most relevant information about the different options for the destruction of defective cells in their article. Researchers paid special attention to available data on non-apoptotic methods of cell death, because it was previously believed that apoptosis was the main way of killing a cell. In this regard, the study of non-apoptotic mechanisms was not a popular area, although it is discoveries in this area that can create the prerequisites for the emergence of new methods of treating tumors.

Laboratory staff hypothesized that the combination of different cell death options will have the greatest effect in the treatment of various diseases. In this case, the suppression of one mechanism will push the cell to activate another, more “suitable” one, which will depend on the particular case. For example, lung adenocarcinoma cells are characterized by a high level of autophagy and resistance to chemotherapeutic drugs. Suppression of autophagy makes this type of tumor more sensitive to treatment.

“The modulation of stress-adaptive reactions and non-apoptotic mechanisms of cell death makes it possible, in particular, to significantly increase the effectiveness of cancer treatment and minimize the side effects of chemotherapy or radiation therapy,” says Professor Boris Zhivotovsky. Thus, the development of scientific knowledge regarding these processes will allow the development of the safest and most effective approaches to the treatment of serious diseases.

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