Evaluation of the effectiveness of the combined effect of ionizing radiation of different quality and doxorubicin on HeLa cells

«Radiation and Risk», 2025, vol. 34, No. 1, pp.128-136

DOI: 10.21870/0131-3878-2025-34-1-128-136

Authors

Melnikova A.A. – Post. Student, Res. Assistant of A. Tsyb MRRC. Contacts: 1 Studgorodok, Obninsk, Kaluga region, Russia, 249039. Tel.: +7 (920) 882-15-74; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Baldov D.A. – Master's Student
Sokolova A.D. – Master's Student
Shkavrov S.V. – Associate Prof., C. Sc., Chem.
Komarova L.N. – Prof., D. Sc., Biol. IATE MEPhI.
¹ Obninsk Institute for National Research Nuclear University MEPhI, Obninsk
²A. Tsyb MRRC, Obninsk

Abstract

Currently, experimental and medical radiology is faced with the need to solve an acute problem – the search for new promising methods of treating tumor diseases. In this regard, it seems relevant both from the point of view of practical application in medicine and from the point of view of fundamental knowledge to conduct a study to find new combinations of the action of ionizing radiation with different LET with anticancer drugs of DNA-directed action on human tumor cells. The aim of the work is to evaluate the effects of the combined action of ¹²C ions and gamma radiation together with doxorubicin on the ability of Hela cells to form colonies. The cells were irradiated with ¹²C ions on a U-70 synchrotron at doses of 1, 2, 4 Gy in an aqueous phantom with an average energy of 450 MeV/nucleon. The average LET of radiation at the initial site was 11 keV/μm, at a peak of 120-140 keV/μm. The irradiation was also carried out at the “GUR-120” gamma radiation facility (source of ionizing radiation ⁶⁰Co, E=1.25 MeV). The dose rate is 0.9 Gy/min. Radiation doses: 1, 2, 4, 6 Gy. An antitumor antibiotic of the anthracycline series doxorubicin at a concentration of 0.004 mg/ml was selected as a chemical agent. Based on these survival curves, the coefficient of interaction was calculated. When combined with gamma radiation in the studied dose range with doxorubicin, an antagonistic effect is observed (k=0.44+-0.07). The synergistic nature of the interaction was observed under the action of ¹²C ions (k=1.40+-0.04). The obtained results of the combined action of the agents used may have important practical and theoretical significance for understanding the mechanism of combined exposure to ionizing radiation of different quality and the chemotherapy drug doxorubicin.

Key words
radiobiology, ¹²C ions, doxorubicin, gamma radiation, cervical cancer cells HeLa, synergism, antagonism, clonogenicity, radiology.

References

1. Trofimova O.P., Tkachev S.I., Yur’yeva T.V. Past and present of radiotherapy in management of malignan-cies. Klinicheskaya onkogematologiya. Fundamental’nyye issledovaniya i klinicheskaya praktika – Clinical Oncohematology. Basic Research and Clinical Practice, 2013, vol. 6, no. 4, pp. 355-364. (In Russian).

2. Losev D.V. Lomanov M.F., Chernyayev A.P. An analytical approximation of spread-out Bragg peak. Preprint MSU, 2003, no. 16, pp. 1-31. (In Russian).

3. Chaulin A.M., Grigor’yeva Yu.V. Proarhythmic effects of doxorubicin (literature review). Izvestiya vysshikh uchebnykh zavedeniy. Povolzhskiy region. Meditsinskiye nauki – University Proceedings. Volga region. Medical Sciences, 2020, vol. 3, no. 55, pp. 118-132. (In Russian).

4. Loeffler J.S., Durante M. Charged particle therapy – optimization, challenges and future direction. Nat. Rev. Clin. Oncol., 2012, vol. 10, no. 7, pp. 411-424.

5. Zhurakovskaya G.P., Petin V.G. Principles of mathematical modeling of combined effects in biology and medicine. Review of the literature. Radiatsiya i risk – Radiation and Risk, 2015, vol. 24, no. 1, pp. 61-73. (In Russian).

6. Rini F.J., Hall E.J., Marino S.A. The oxygen enhancement ratio as a function of neutron energy with mam-malian cells in culture. Radiat. Res., 1979, vol. 78, no. 1, pp. 25-23.

7. Alyasova A.V., Vedunova M.V., Mishchenko T.A., Terent’yev I.G., Tsybusov S.N., Kontorshchikova K.N. Effect of ozone and doxorubicin on the viability and morphology of malignant hepatic cells. Sovremennye Tehnologii v Medicine – Modern Technologies in Medicine, 2016, vol. 8, no. 2, pp. 84-89. (In Russian).

8. Bakina O.V., Svarovskaya N.V., Miller A.A., Lozhkomoyev A.S., Avgustinovich A.V., Dobrodeyev A.Yu., Spirina L.V., Afanasyev S.G. Synergistic effect of antitumor activity of doxorubicin and bicomponent nanostructures based on aluminum oxide. Sibirskiy onkologicheskiy zhurnal – Siberian Journal of Oncology, 2020, vol. 19, no. 2, pp. 82-89. (In Russian).

9. Kontorshchikova K.N., Vedunova M.V., Makarova E.S., Orlov B.Yu. The influence of doxorubicin, ozone and oxygen on viability of normal and malignant liver cells in culture. Bioradikaly i antioksidanty – Bioradicals and Antioxidants, 2016, vol. 3, no. 1, pp. 15-17. (In Russian).

10. Guda K., Natale L., Markowitz S. An improved method for staining cell colonies in clonogenic assays. Cytotechnology, 2007, vol. 54, pp. 85-88.

11. Petin V.G., Zhurakovskaya G.P., Komarova L.N. Radiobiological bases of synergistic interaction in the bio-sphere. Moscow, Geos, 2012. 219 p. (In Russian).

12. Petin V.G., Zhurakovskaya G.P., Pantyukhina A.G., Rassokhina A.V. Small doses and synergistic interac-tion of environmental factors. Radiatsionnaya biologiya. Radioekologiya – Radiation Biology. Radioecology, 1999, vol. 39, no. 1, pp. 113-126. (In Russian).

13. Petin V.G., Komarov V.P. A quantitative description of the modification radiosensitivity. Moscow, Ener-goatomizdat, 1989. 192 p. (In Russian).

14. Petin V.G., Komarova L.N. Significance of synergistic interaction of ionizing radiation and other unhealthy factors for strengthening of Chernobyl accident consequences. Radiatsiya i risk – Radiation and Risk, 2006, vol. 15, no. 1-2, pp. 85-113. (In Russian).

15. Melnikova A.A., Baldov D.A., Komarova L.N. Experimental research of the biological effect of 12C and 60C ions on hepatocarcinoma cells. Medline.ru. Rossiyskiy biomeditsinskiy zhurnal – Medline.ru. Russian Biomedical Journal, 2023, vol. 24, no. 1, pp. 597-609. (In Russian).

16. Gulidov I.A. Perspectives of development of hadron radiation therapy. Radiatsionnaya onkologiya I yadernaya medicina – Radiation Oncology and Nuclear Medicine, 2013, no. 1, pp. 34-39. (In Russian).

17. Komarova L.N., Mel’nikova A.A., Baldov D.A. Synergetic effects of the combined action of carbon ions and the chemotherapy drug doxorubicin on HeLa cancer cells. Izvestiya vysshikh uchebnykh zavedeniy. Yadernaya energetika – Nuclear Energy and Technology, 2021, no. 3, pp. 158-168. (In Russian).

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