Dependence of the RBE of densely ionizing radiation from radiosensitivity and stage of cell growth

«Radiation and Risk», 2020, vol. 29, No. 2, pp.57-66

DOI: DOI: 10.21870/0131-3878-2020-29-2-57-66

Authors

Vorobey O.A. – Researcher. Contacts: 4 Korolyov str., Obninsk, Kaluga region, Russia, 249035. Tel: +7(484) 39-93297-7008; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Petin V.G. – Lead. Researcher, D. Sc., Biol., Prof.
Tolkaeva M.S. – Engineer. A. Tsyb MRRC.
Filimonova A.N. – Lab. Assistant. NMRRC.

¹ A. Tsyb MRRC, Obninsk
² NMRRC Russian Ministry of Health, Moscow

Abstract

The analysis of the patterns of densely ionizing radiation RBE display is an urgent problem for the radiological substantiation of the hadron therapy of human tumors that is being actively introduced into practice. To experimentally study the dependence of RBE of densely ionizing radiation on radiosensitivity and the stage of cell growth; confirm the participation of cell repair processes in the formation of alpha particles RBE. The experiments used wild-type haploid and diploid yeast cells Saccharomyces cerevisiae and their radiosensitive mutants, which are incapable of recovering from radiation damage induced by sparsely and densely ionizing radiation. Cells were irradiated in stationary and logarithmic growth stages. It was shown that for haploid yeast cells exposed to ⁶⁰Co gamma-rays and ²³⁹Pu alpha-particles in the stationary stage of growth RBE was 2.3 and did not depend on the dose of ionizing radiation. On the contrary, at the stage of cell division, the RBE values increased from 1.9 to 6 with dose increase. When diploid cells are irradiated in the stationary stage of growth, RBE=5.4 and almost did not depend on dose while at the stage of cell reproduction RBE of alpha-particles sharply increased from 4.5 to 8.7 with dose decrease. For radiosensitive mutants unable to recover from DNA damage, the RBE of alpha-particles weakly depended on cell ploidy and decreased slightly upon irradiation of dividing cells (RBE=1.6) as compared to irradiation of cells in the stationary growth stage (RBE=2.2). It is concluded that the results obtained are consistent with the point of view that the RBE of densely ionizing radiation is determined not only by the probability of the primary damage production at the physicochemical stage of radiation interaction with cellular structures, but also by the cell ability to recover from sublethal and potentially lethal damage at biochemical stage of their fixation. It is stressed the need to take into account the obtained variability of RBE values of high LET radiation at the interpretation of experiments with cultured mammalian cells. Since the processes of alpha-particles interaction with living matter are qualitatively identical to the interaction of protons produced in tissues during neutron irradiation, the results obtained here should be taken into account when analyzing the effectiveness of antitumor radiation therapy of hadron radiation – neutrons, protons and other heavy charged particles.

Key words
relative biological efficiency (RBE), yeast cells, gamma-rays, alpha-particles, cellploidy, stage of growth, cell recovery, DNA repair, radiosensitive mutants, linear energy transfer (LET), radiation damage.

References

1. Yarmonenko S.P., Konoplyannikov A.G., Weinson A.A. Klinicheskaya radiobiologiya [Clinical radiobiology]. Moscow, Medicine, 1992. 320 p.

2. Terapevticheskaya radiologiya [Therapeutic Radiology]. Eds.: A.F. Tsyb, Yu.S. Mardynsky. Moscow, OOO MK, 2010. 552 p.

3. Alper T. Cellular Radiobiology. London, Cambridge University Press, 1979. 320 p.

4. Krasavin E.A. Radiobiological research at JINR’s accelerators. Phys.-Usp., 2016, vol. 59, no. 4, pp. 411-418.

5. Li D.E. Dejstvie radiacii na zhivye kletki [Effect of radiation on living cells]. Moscow, Gosatomizdat, 1963. 288 p.

6. Petin V.G. Geneticheskij kontrol' modifikacij radiochuvstvitel'nosti kletok [Genetic control of cell radiosensitivity modifications]. Moscow, Energoatomizdat, 1987. 208 p.

7. Belkina S.V., Petin V.G., Khrachkova A.V. The influence of pre-radiation conditions of cultivation of bacte-ria on the RBE of densely ionizing radiation. Mezhdunarodnyy zhurnal prikladnykh i fundamental’nykh issledovaniy – International Journal of Applied and Fundamental Research, 2016, no. 10 (p. 4), pp. 577-581. (In Russian).

8. Pohlit W.E., Schäfer M. Recovery and repair in yeast cells after irradiation with densely ionizing particles. Biological Effects of Neutron Irradiation. Vienna: IAEA, 1974, pp. 177-184.

9. Petin V.G. RBE densely ionizing radiation and cell repair. Medicinskaya radiologiya – Medical Radiology, 1977, vol. 22, no. 10, pp. 8-12. (In Russian).

10. Krasavin E.A. Problemy RBE i reparatsiya DNK. Moskva, Ehnergoatomizdat [OBE problems and DNA repair]. Moscow, Energoatomizdat, 1989. 192 p.

11. Petin V.G., Zhurakovskaya G.P., Komarova L.N. Radiobiologicheskie osnovy sinergicheskih vzaimodeistvii v biosfere [Radiobiological basis of synergistic interaction in biosphere]. Moscow, GEOS, 2012. 219 p.

12. Luchnik A.N., Glaser V.M., Shestakov S.V. Repair of DNA double-strand breaks requires two homologous DNA duplexes. Mol. Biol. Rep., 1977, vol. 3, no. 6, pp. 437-442.

13. Frankenberg D. Interpretations of the dose and LET dependence of RBE values for lethal lesions in yeast cells. Radiat. Res., 1984, vol. 97, no. 2, pp. 329-340.

14. Saeki T., Machida I., Nakai S. Genetic control of diploid recovery after gamma-irradiation in the yeast Sac-charomyces cerevisiae. Mutat. Res., 1980, vol. 73, no. 2, pp. 251-265.

15. Haynes R.H. The interpretation of microbial inactivation and recovery phenomena. Radiat. Res., 1966, vol. Suppl. 6, pp. 1-29.

16. Hesslewood I.P. DNA strand breaks in resistant and sensitive murine lymphoma cells detected by the hydroxylapatite chromatographic technique. Int. J. Radiat. Biol., 1978, vol. 34, no. 5, pp. 461-469.

17. Tobias C.A., Blakely E.A., Chang P.Y., Lommel L., Roots R. Response of sensitive human ataxia and resistant T-1 cell lines to accelerated heavy ions. Br. J. Cancer Suppl., 1984, vol. 6, pp. 175-185.

18. Frankenberg-Schwager M., Frankenberg D., Harbich R. Repair of DNA double-strand breaks as a determinant of RBE of alpha particles. Br. J. Cancer Suppl., 1984, vol. 6, pp. 169-173.

19. Weichselbaum R.R. Radioresistant and repair proficient cells may determine radiocurability in human tumors. Int. J. Radiat. Oncol. Biol. Phys., 1986, vol. 12, no. 4, pp. 637-639.

20. Martin N.M. DNA repair inhibition and cancer therapy. J. Photochem. Photobiol. B. 2001, vol. 63, no. 1-3, pp. 162-170.

Full-text article (in Russian)