Reactions of normal and tumor cells and tissues to hyperthermia in combination with ionizing radiation. Review

«Radiation and Risk», 2018, vol. 27, No. 4, pp.141-154

DOI: 10.21870/0131-3878-2018-27-4-141-154


Kabakov A.E. – Head of Lab., C. Sc., Biol.
Lebedeva T.V. – Lead. Researcher, C. Sc., Biol.
Anokhin Yu.N. – Head of Dep., C. Sc., Med. Contacts: 1, Studgorodok, Obninsk, Kaluga region, Russia, 249036. Tel.: +7-910-542-97-30; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .

1A. Tsyb MRRC, Obninsk
2Obninsk Institute for Nuclear Power Engineering, Obninsk


The review presents an analysis of literature data on the modifying effect of hyperthermia (HT) on the radiation response of normal and tumor cells and tissues, as well as on the use of HT to increase the radiosensitivity of tumors. The analyzed data indicate that the radiosensitizing effects of HT are manifested in the additive or synergistic enhancement of cytotoxicity in irradiated bioobjects. The degree of such enhancement depends on the level of heating, radiation dose, the sequence of the exposures and the interval between them, types of tissue, etc. The radiosensitizing effects of HT are manifested not only on tumors, but also on normal cells and tissues too. This circumstance requires determination of the therapeutic gain factor in different cases of application of the thermotherapy of tumors. Heatshock proteins (HSPs), which are one of the factors of tumor resistance to thermo, chemo and radiotherapy, are actively involved in cellular reactions to HT and radiation exposure. It is shown that the functioning of HSP90 is necessary for the postradiation repair of nuclear DNA breaks. In addition, HSP90, HSP70 and HSP27 are powerful suppressors of apoptosis and help the stressed cell to reactivate or degrade stressdenatured proteins. In the case of a combination of HT and radiation, these HSPs form complexes with denatured intracellular proteins and can no longer act as radioprotectors and blockers of apoptosis. Thus, recruitment of HSPs to protect against the proteotoxic effects of HT occurs to the detriment of HSPmediated radioresistance of cancer cells and, consequently, contributes to their radiosensitization. However, the induction and transient increase in the levels of HSP90, HSP70 and HSP27 in cells that have survived HT can make them for some period thermotolerant and more radioresistant that should be taken into consideration in the case of consequtive combining HT and radiation therapy.

Key words
Ionizing radiation, heat shock proteins, radiosensitivity, hyperthermia, extra- and intracellular рО2 and pH, blood flow, thermal sensitivity, therapeutic gain, therapy of tumors, thermotolerance.


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