employee
Institute for Biomedical Problems
employee
A.I. Burnasyan Federal Medical Biophysical Center (FMBC) FMBA
employee
Russian Federation
employee
Institute of Biomedical Problems, Russian Academy of Sciences (Junior Researcher)
employee
Russian Federation
employee
Institute of Biomedical Problems, Russian Academy of Sciences (Junior Researcher)
Russian Federation
employee
Russian Federation
GRNTI 76.03 Медико-биологические дисциплины
GRNTI 76.33 Гигиена и эпидемиология
OKSO 14.04.02 Ядерные физика и технологии
OKSO 31.06.2001 Клиническая медицина
OKSO 31.08.08 Радиология
OKSO 32.08.12 Эпидемиология
BBK 51 Социальная гигиена и организация здравоохранения. Гигиена. Эпидемиология
BBK 534 Общая диагностика
TBK 5708 Гигиена и санитария. Эпидемиология. Медицинская экология
TBK 5712 Медицинская биология. Гистология
TBK 5734 Медицинская радиология и рентгенология
TBK 6212 Радиоактивные элементы и изотопы. Радиохимия
The article contains an analysis of literature data and the author’s own results on the radiobiological effects of protons at the cellular, systemic (intercellular) and organismic levels, as applied to the practical tasks of radiation therapy of oncological diseases and the protons effects on the astronauts’ organism. It is established that the proton RBE is a variable value, depending on the LET of the particles, the amount and dose rate, the presence or absence of oxygen. Proton RBE varies depending on the object of study, the type of tissue, proton energy and particle penetration depth, as well as the method for evaluating the biological efficiency of protons. which corresponds to general radiobiology. In particular, it has been shown that the RBE of protons adopted in radiation therapy at the level of 1.1 is conditional. A firmly established and repeatedly confirmed is an increase in RBE with a decrease in proton energy and, accordingly, an increase in LET. The use of elements of the physical protection of a spacecraft during exposure to protons with an energy of 170 MeV leads to an increase in LET and RBE of protons in terms of the cellularity of the bone marrow. Pharmacological agents effective in photon irradiation are also effective when exposed to a proton beam. It has been shown that natural melanin pigment and recombinant manganese superoxide dismutase helps to preserve and accelerate the resumption of blood formation in animals irradiated by protons. The Grippol vaccine increases radioresistance during proton irradiation. Neuropeptide Semax has a positive effect on the central nervous system and the strength of the forepaws of animals irradiated with protons at Bragg’s peak.
protons, RBE, Bragg peak, central nervous system, hematopoiesis, chromosomal aberrations, survival, radioprotective agents, radiation therapy, space radiation, mice, rat
1. Paganetti H. Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and liners energy transfer. Phys Med Biol. 2014 Nov 21;59(22): R419-72. DOI:https://doi.org/10.1088/0031-9155/59/22/R419.
2. Gazenko OG, Calvin M. Foundations of Space Biology and Medicine. Vol I. Space as a Habitat. Moscow: Nauka; 1975; 430 p. (Russian).
3. Nurlybaev K, Martinyuk Yu, Karakash A. Radiation Protection in Radiotherapy Using Electron Accelerators. ANRI. 2014;1(76):15-21. (Russian).
4. Grigor’ev YuG. The biological effect of high-energy protons. Moscow: Atomizdat. 1967; 508 p. (Russian).
5. Grigor’ev AI, Krasavin EA, Ostrovskij MA. Galactic heave charged particles damaging effect on biological structures. Neuroscience and Behavioral Physiology - Sechenov Physiology Journal. 2013; 99(3); 273-80. (Russian).
6. Fedorenko BS. Radiobiological effects of corpuscular radiation: radiation safety of space flight. Moscow: Nayka. 2006; 189 p. (Russian).
7. Cucinotta A, Durante M, Loeffler J. Editorial: Charged Particles in Oncology. Front Oncol. 2017 Dec 8;7:301. DOI:https://doi.org/10.3389/fonc.2017.00301.
8. Durante M, Tommasino F. Proton radiobiology. Cancers (Basel). 2015 Feb 12;7(1):353-81. DOI:https://doi.org/10.3390/cancers7010353.
9. Girdhani S, Sachs R, Hlatky L. Biological Effects of proton radiation: what we know and don’t know. Radiat Res. 2013 Mar;179(3):257-72. DOI:https://doi.org/10.1667/RR2839.1.
10. Butomo NV, Grebenyuk AN, Legeza VN, et al. Fundamentals of Medical Radiobiology. SPb.: Foliant. 2004; 258 p. (Russian).
11. Belli M, Bettega D, Calzolari P, et al. Inactivation of human normal and tumor cells irradiated with low energy protons. Int J Radiat Biol. 2000 Jun;76(6):831-9.
12. Ushakov I.B, Shtemberg A.S. The problems of studying the effects of far long-duration space mission factors on the higher nervous activity in model experiments with animals. Aerospace and Environmental Medicine. 2012; 46(1):5-16. (Russian).
13. Parihar VK, Allen B, Tran KK, et al. What happens to your brain on the way to Mars. Sci Adv. 2015 May 1;1(4). DOI:https://doi.org/10.1126/sciadv.1400256.
14. Pyatkin EK, Baranov AE, Filyushkin IV, et al. Estimation of the dose and uniformity of radiation in acute human radiation lesions using the analysis of chromosomal aberrations. Guidelines. Moscow: USSR Ministry of Health, 1988; 25 p. (Russian).
15. Govorun RD, Deperas-Kaminska M, Zaitseva EM, et al. Study of chromosomal abnormalities in human cells after irradiation with a therapeutic beam of protons of the phasotron of the Joint Institute for Nuclear Research. Letters to ECHA. 2006;3(1):92-101. (Russian).
16. Dorozhkina OV, Bulynina TM, Ivanov AA. Effect of individual and group housing of mice on the level of radioresistance. Saratov. Nauch.-Med. Zh. 2015;60(5):653-6. (Russian).
17. Fedorenko BS, Shevchenko VA, Snigireva GP, et al. Cytogenetic studies of blood lymphocytes of cosmonauts after long-ter, space flights. Radiation Biology. Radioecology. 2000;40(5):596-602. (Russian).
18. Nugis VYu. Estimation of radiation dose from cytogenetic studies of peripheral blood and bone marrow. In: Radiation damage of humans. Ed. L.A. Ilyin. Moscow: Izd. At. 2001. Vol. 2:249-53 (Russian).
19. Hayata I. Biological dosimetry by chromosome analysis. Radiation and Risk. 1996;(7):72-5.
20. Voskanian KSh, Mitsyn GV, Gaevsky VN. Effectiveness of the biological action of protons and gamma-radiation on cells C3H10T1/2. Aviakosm Ekolog Med. 2005;39(5):50-3. (Russian).
21. Tang JT, Inoue T, Yamazaki H, et al. Comparison of radiobiological effective depths in 65 MeV modulated proton beams. Br J Cancer. 1997;76(2):220-5.
22. Calugaru V, Nauraye C, Noel G, et al. Radiobiological characterization of two therapeutic proton beams with different initial energy spectra used at the Institute Curie Proton Therapy Center in Orsay. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):1136-43. DOI:https://doi.org/10.1016/j.ijrobp.2010.09.003.
23. Sgura A, Antoccia A, Cherubini R, et al. Micronuclei, CREST-positive micronuclei and cell inactivation induced in Chinese hamster cells by radiation with different quality. Int J Radiat Biol. 2000 Mar;76(3):367-74.
24. Gerelchuluun A, Hong Z, Sun L et al. Induction of in situ DNA double-strand breaks and apoptosis by 200 MeV protons and 10 MV X-rays in human tumour cell lines. Int J Radiat Biol. 2011 Jan;87(1):57-70. DOI:https://doi.org/10.3109/09553002.2010.518201.
25. Di Pietro C, Piro S, Tabbi G, Ragusa M, Di Pietro V, Zimmitti V, et al. Cellular and molecular effects of protons: apoptosis induction and potential implications for cancer therapy. Apoptosis. 2006 Jan;11(1):57-66.
26. Green LM, Tran DT, Murray DK, et al. Response of thyroid follicular cells to gamma irradiation compared to proton irradiation: II. The role of connexin 32. Radiat Res. 2002 Oct;158(4):475-85.
27. Ristic-Fira AM, Todorovic DV, Koricanac LB, et al. Response of a human melanoma cell line to low and high ionizing radiation. Ann NY Acad Sci. 2007 Jan;1095:165-74.
28. Lee KB, Lee JS, Park JW, et al. Low energy proton beam induces tumor cell apoptosis through reactive oxygen species and activation of caspases. Exp Mol Med. 2008 Feb 29;40(1):118-29.
29. Pawlik TM, Keyomarsi K. Role of cell cycle in mediating sensitivity to radiotherapy. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):928-42.
30. Moertel H, Georgi JC, Distel L, et al. Effects of low energy protons on clonogenic survival, DSB repair and cell cycle in human glioblastoma cells and B14 fibroblasts. Radiother Oncol. 2004 Dec;73 Suppl 2:S115-8.
31. Antoccia A, Sgura A, Berardinelli F, et al. Cell cycle perturbations and genotoxic effects in human primary fibroblasts induced by low-energy protons and X/gamma-rays. J Radiat Res. 2009 Sep;50(5):457-68.
32. Desouky O, Ding N, Zhou G. Targeted and non-targeted effects of ionizing radiation. J Radiat Res Appl Sci. 2015;8(2):247-54. DOI:https://doi.org/10.1016/j.jrras.2015.03.003.
33. Childs SK, Kozak KR, Friedmann AM, et al. Proton radiotherapy for parameningeal rhabdomyosarcoma: clinical outcomes and late effects. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):635-42. DOI:https://doi.org/10.1016/j.ijrobp.2010.11.048.
34. Sheets NC, Goldin GH, Meyer AM, et al. Intensity-modulated radiation therapy, proton therapy, or conformal radiation therapy and morbidity and disease control in localized prostate cancer. JAMA. 2012. Apr 18;307(15):1611-20. DOI:https://doi.org/10.1001/jama.2012.460.
35. Yarmonenko SP, Weinson AA. Radiobiology of Humans and Animals. Moscow: Vysshaya shkola. 2004. 549 p. (Russian).
36. Gerweck LE, Kozin SV. Relative biological effectiveness of proton beam in clinical therapy. Radiother Oncol. 1999 Feb;50(2):135-42.
37. Skarsgard LD. Radiobiology with heavy charged particles: a historical review. Phys Med Biol. 1998 Jul;14 Suppl 1:1-19.
38. Wambersie A, Menzel HG, Andreo P, et al. Isoeffective dose: a concept for biological weighting of absorbed dose in proton and heavier-ion therapies. Radiat Prot Dosimetry. 2011 Feb;143(2-4):481-6. DOI:https://doi.org/10.1093/rpd/ncq410.
39. Kase Y, Yamashita W, Matsufuji N, et al. Microdosimetric calculation of relative biological effectiveness for design of therapeutic proton beams. J Radiat Res. 2013 May;54(3):485-93. DOI:https://doi.org/10.1093/jrr/rrs110.
40. Gueulette J, Bohm L, Slabbert JP, et al. Proton relative biological effectiveness (RBE) for survival in mice alter thoracic irradiation with fractionated doses. Int J Radiat Oncol Biol Phys. 2000 Jul 1;47(4):1051-8.
41. Tilly N, Johansson J, Isacsson U, et al. The influence of RBE variations in a clinical proton treatment plan for a hypopharynx cancer. Phys Med Biol. 2005 Jun 21;50(12):2765-77.
42. Giovannini G, Böhlen T, Cabal G, et al. Variable RBE in proton therapy: comparison of different model predictions and their influence on clinical-like scenarios. Radiat Oncol. 2016 May 17;11:68. DOI:https://doi.org/10.1186/s13014-016-0642-6.
43. Matsumoto Y, Matsuura T, Wada M, et al. Enhanced radiobiological effects at the distal end of a clinical proton beam: in vitro study. J Radiat Res. 2014 Jul;55(4):816-22. DOI:https://doi.org/10.1093/jrr/rrt230.
44. Tronov VA, Vinogradova YuV, Poplinskaya VA, et al. Investigation of the adaptive response of the retina in mice to proton irradiation: connection with DNA repair and photoreceptor cell death. Letters to ECHA. 2015;12(1):241-55 (Russian).
45. Sapetsky AO, Ushakov IB, Sapetski NV, et al. Radiation neurobiology of distant space flights. Successes of Modern Biology. 2017;137(2):165-94 (Russian).
46. Taketa ST, Castle BL, Howard WH et al. Effects of acute exposure to high-energy protons on primates. Radiat Res Suppl. 1967;7:336-59.
47. Bushmanov AYu, Torubarov FS. Neurological aspects of radiation damage. Radiation Medicine. Ed. Ilyin L.A. Vol. 2. - Moscow: Izd. At. 2001; 275-305. (Russian).
48. Darenskaya NG. Reaction of the hematopoietic system. Radiation Medicine. Vol. 1. Moscow: Izd. At. 2004. P. 295-307. (Russian).
49. Darenskaya NG, Kozlova LB, Akoev IG, Nevskaya TF. Relative Biological Efficiency of Radiation. The Time Factor of Exposure. Moscow: Atomizdat. 1968. 376 p. (Russian).
50. Seraya VM. Investigation of hematopoietic systems in experimental animals irradiated with 120 MeV protons: PhD Med: Moscow. 1970. 155 p. (Russian).
51. Ryzhov NI. Biological Action of Protons. In: Ugolev A.M. editors. Biophysical bases of the action of cosmic radiation and accelerator radiation. L.: Science. 1989;60:170-8. (Russian).
52. Shmakova NL, Yarmonenko SP. Cytological analysis of the action of high-energy protons: 1. Cellular degeneration and mitotic activity of the bone marrow of mice subjected to proton irradiation. Radiobiology. 1963;3:291-3. (Russian).
53. Ware JH, Sanzari J, Avery S, et al. Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice. Radiat Res. 2010 Sep;174(3):325-30. DOI:https://doi.org/10.1667/RR1979.1.
54. Sanzary JK, Wan XS, Krigsfeld GS, et al. The effects of gamma and proton radiation exposure on hematopoietic cells counts in the ferret model. Gravit Space Res. 2013 Oct;1(1):79-94.
55. Rithidech KN, Honikel LM, Reungpatthanaphong P, et al. Effects of 100 MeV protons delivered at 0,5 or 1 cGy/min on the in vivo induction of early and delayed chromosomal damage. Mutat Res. 2013 Aug 30;756(1-2):127-40. DOI:https://doi.org/10.1016/j.mrgentox.2013.06.001.
56. Gridley DS, Pecaut MJ, Dutta-Roy R, Nelson GA. Dose and dose rate effects of whole-body proton irradiation on leukocyte populations and lymphoid organs: Part I. Immunol Lett. 2002 Jan 1;80(1):55-66.
57. Vorozhtsova SV, Bulynina TM, Molokanov AG, Ivanov AA. Cytogenetic damage to the corneal epithelium of mice due to the in vivo exposure to ionizing radiation with different levels of linear energy transfer. Aviakosm Ekolog Med. 2015;49(1):50-6 (Russian).
58. Ando K, Furusawa Y, Suzuki M, et al. Relative Biological Effectiveness of the 235 MeV Proton Beams at the National Cancer Center Hospital East. J Radiat Res. 2001 Mar;42(1):79-89.
59. Ivanov AA, Molokanov AG, Ushakov IB, et al. Radiobiological effects of total mice irradiation with bragg’s peak protons. Aviakosm Ekolog Med. 2013;47(6):49-54 (Russian).
60. Ivanov AA, Bulynina TM, Molokanov AG, et al. Demonstration of likelihood of the negative effect of physical protection during total proton irradiation of mice. Aviakosm Ekolog Med. 2015;49(4):26-30. (Russian).
61. Maks CJ, Wan XS, Ware JH, et al. Analysis of White Blood Cell Counts in Mice after Gamma- or Proton-Radiation Exposure. Radiat Res. 2011 Aug;176(2):170-6. DOI:https://doi.org/10.1667/RR2413.1.
62. Gueulette J, Slabbert JP, Böhm L, et al. Proton RBE for early intestinal tolerance in mice after fractionated irradiation. Radiother Oncol. 2001 Nov;61(2):177-84.
63. Ilyin LA, Rudny NM, Suvorov NN, Chernov GA. Indralin is an emergency radio protector. Anti-radiation properties, pharmacology, mechanism of action, clinic. Moscow. 1994. 436 p. (Russian).
64. Vasin MV. Means of Prevention and Treatment of Radiation Injuries. Moscow: VTSMK Protection. 2006. 340 p. (Russian).
65. Zherebin YuM, Bondarenko NA, Makan SYu, et al. Pharmacological properties of enomelanin pigments. Reports of the Academy of Sciences of the Ukrainian SSR. Series 5. 1984;(3):64-7. (Russian).
66. Zorina ZA, Poletaeva II. Zoopsychology. Elementary thinking of animals: study guide. Moscow: Aspect-Press. 2008. 320 p. (Russian).
67. Ivanov AA, Andrianova IE, Bulynina TM, et al. Pharmacological effects of melanin in irradiated mice. Medical Radiology and Radiation Safety. 2015;60(5):5-11. (Russian).
68. Ivanov AA, Abrosimova AN, Bulynina TM. Effects of the vaccine Grippol on resistance of mice after irradiation by protons. Saratov. Nauch.-Med. Zh. 2015;11(4):656-8. (Russian).
69. Ambesi-Impiombato FS, Ivanov AA, Mancini A, et al. Effect of recombinant manganese superoxide dismutase (rMnSOD) on the hematologic status in mice irradiated by protons. Medical Radiology and Radiation Safety. 2014;59(6):5-11.
70. Lyakhova KN, Ivanov AA, Molokanov AG, et al. Effect of neuropeptide semax on the exploratory behavior reaction and strength of skeletal musculature of proton-irradiated mice. Aviakosm Ekolog Med. 2018;52(4):71-6. (Russian).
