Modification of the Effect of Pharmacological Agents, Ionizing Radiation and Hyperthermia on Tumor Cells by Vitamin E

AbstractThe lung is one of the most sensitive tissues to ionizing radiation, thus, radiation-induced lung injury (RILI) stays a key dose-limiting factor of thoracic radiotherapy. However, there is still little progress in the effective treatment of RILI. Ras-related C3 botulinum toxin substrate1, Rac1, is a small guanosine triphosphatases involved in oxidative stress and apoptosis. Thus, Rac1 may be an important molecule that mediates radiation damage, inhibition of which may produce a protective effect on RILI. By establishing a mouse model of radiation-induced lung injury and orthotopic lung tumor-bearing mouse model, we detected the role of Rac1 inhibition in the protection of RILI and suppression of lung tumor. The results showed that ionizing radiation induces the nuclear translocation of Rac1, the latter then promotes nuclear translocation of P53 and prolongs the residence time of p53 in the nucleus, thereby promoting the transcription of Trp53inp1 which mediates p53-dependent apoptosis. Inhibition of Rac1 significantly reduce the apoptosis of normal lung epithelial cells, thereby effectively alleviating RILI. On the other hand, inhibition of Rac1 could also significantly inhibit the growth of lung tumor, increase the radiation sensitivity of tumor cells. These differential effects of Rac1 inhibition were related to the mutation and overexpression of Rac1 in tumor cells.

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New pharmacological means of radiation protection (literature review)

JOURNAL OF THE NATIONAL ACADEMY OF MEDICAL SCIENCES OF UKRAINE ◽

10.37621/jnamsu-2019-3-268-277 ◽

2019 ◽

Author(s):

Nataliya Uzlenkova

Keyword(s):

Bone Marrow ◽

Ionizing Radiation ◽

Literature Review ◽

Radiation Exposure ◽

Progenitor Cells ◽

Radiation Protection ◽

Acute Radiation ◽

Biologically Active ◽

Pharmacological Agents ◽

Methodological Approaches

The review systematized the current data on new classes of pharmacological compounds and biologically active substances in the field of radiation protection in Ukraine, as well as abroad. Methodological approaches and the importance of using appropriate animal models in the development of new pharmacological drugs for radiation protection are described, specifically in the cases when it is impossible to conduct full clinical trials on patients. Current views on the division of pharmacological agents into radioprotectors, radiomitigators, and therapeutic radiation protection agents are examined. The changes in the hematopoietic tissue, gastrointestinal tract and neurovascular system that occur after acute radiation exposure are also described. Particular attention is paid to pharmacological agents that can protect against acute exposure to ionizing radiation by limiting the risk of radiation mortality from the hematological and gastrointestinal forms of radiation syndrome. Results of the effectiveness of tolerant antioxidants with a wide spectrum of biological activity as promising agents for the prevention of acute and delayed radiation-induced pathology, in particular, in lung tissue, are presented. Possible molecular mechanisms of the radioprotective effect of pharmacological compounds on experimental models of total and local radiation exposure are discussed. The effectiveness of the therapeutic use of growth factors and recombinant cytokines in acute bone marrow suppression аfter accidental radiation exposure is shown. The possibilities of cell therapy with myeloid progenitor cells mobilized by tocopherol succinate hematopoietic/progenitor cells and bone marrow mesenchymal stromal cells in acute radiation injuries are shown. Special attention is paid to the importance of improving such methodological approaches and regulatory requirements when introducing into practice new radiation protection facilities in Ukraine. Key words: radiation protection, ionizing radiation, pharmacological agents, acute radiation syndrome. For citation: Uzlenkova NE. New pharmacological means of radiation protection (literature review). Journal of the National Academy of Medical Sciences of Ukraine. 2019;25(3) :268–77

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The p53 Protein Family in the Response of Tumor Cells to Ionizing Radiation: Problem Development

Acta Naturae ◽

10.32607/actanaturae.11247 ◽

2021 ◽

Vol 13 (3) ◽

pp. 65-76

Author(s):

Oleg A. Kuchur ◽

Daria O. Kuzmina ◽

Marina S. Dukhinova ◽

Alexandr A. Shtil

Keyword(s):

Signal Transduction ◽

Ionizing Radiation ◽

Radiation Exposure ◽

Tumor Cells ◽

P53 Protein ◽

Intracellular Signal Transduction ◽

Radiation Problem ◽

The Family ◽

Intracellular Signal ◽

Survival Mechanisms

Survival mechanisms are activated in tumor cells in response to therapeutic ionizing radiation. This reduces a treatments effectiveness. The p53, p63, and p73 proteins belonging to the family of proteins that regulate the numerous pathways of intracellular signal transduction play a key role in the development of radioresistance. This review analyzes the p53-dependent and p53-independent mechanisms involved in overcoming the resistance of tumor cells to radiation exposure.

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