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 review represents comparative data on the biological effects of inorganic (HTO) and organic (OBT) compounds of tritium at the molecular, cytogenetic and system levels. The data of the relative biological effectiveness (RBE) of OBT and HTO depending on their distribution in the cells and tissues of the body are presented. Experimental studies show that the calculation of the RBE of tritium compounds at different levels of organization leads to contradictory data. Such observation is associated with the interaction both of HTO and OBT with critical biomolecules in the cells as well as the proliferative activity of different cells and tissues. The experiments revealed that the effectiveness of OBT is much higher than the HTO which is associated with their rapid inclusion in the critical biomolecules such as proteins and DNA with the further formation of a significant biological effect. Based on the recently obtained data in different laboratories on the effect of tritium compounds at the molecular and cellular levels, it is concluded that a new approach for HTO and OBT risk assessment is necessary.
tritium, organic compounds of the tritium, tritium oxide, HTO, OBT, RBE, DNA double-strand breaks, γН2АХ, 3H-thymidine, tritiated water, risk assessment
1. Review of risks from tritium: report of the independent Advisory Group on Ionising Radiation. Chilton: Health Protection Agency, Centre for Radiation, Chemical and Environmental Hazards; 2007.
2. Roch-Lefevre S, Gregoire E, Martin-Bodiot C, Flegal M, Freneau A, Blimkie M, et al. Cytogenetic damage analysis in mice chronically exposed to low-dose internal tritium beta-particle radiation. Oncotarget. 2018;9(44):27397-411.
3. Bannister L, Serran M, Bertrand L, Klokov D, Wyatt H, Blimkie M, et al. Environmentally Relevant Chronic Low-Dose Tritium and Gamma Exposures do not Increase Somatic Intrachromosomal Recombination in pKZ1 Mouse Spleen. Radiat Res. 2016;186(6):539-48.
4. Kim SB, Baglan N, Davis PA. Current understanding of organically bound tritium (OBT) in the environment. J Environ Radioact. 2013;126:83-91.
5. Harrison JD, Khursheed A, Lambert BE. Uncertainties in dose coefficients for intakes of tritiated water and organically bound forms of tritium by members of the public. Radiat Prot Dosimetry. 2002;98(3):299-311.
6. Chao TC, Wang CC, Li J, Li C, Tung CJ. Cellular- and micro-dosimetry of heterogeneously distributed tritium. Int J Radiat Biol. 2012;88(1-2):151-7.
7. Gerweck LE, Kozin SV. Relative biological effectiveness of proton beams in clinical therapy. Radiother Oncol. 1999;50(2):135-42.
8. Skarsgard LD. Radiobiology with heavy charged particles: a historical review. Phys Med. 1998;14 Suppl 1:1-19.
9. Snigireva GP, Khaimovich TI, Nagiba VI. Assessment of relative biological effectiveness of tritium using chromosome aberration frequency in human blood lymphocytes. Radiation Biol Radioecol. 2010;50(6):663-71. (in Russ.)
10. Brooks AL. Chromosome damage in liver cells from low dose rate alpha, beta, and gamma irradiation: derivation of RBE. Science. 1975;190(4219):1090-2.
11. Hamby DM. Uncertainty of the tritium dose conversion factor. Health Phys. 1999;77(3):291-7.
12. Peterson SR, Davis PA. Tritium doses from chronic atmospheric releases: a new approach proposed for regulatory compliance. Health Phys. 2002;82(2):213-25.
13. Lucas JN, Hill FS, Burk CE, Cox AB, Straume T. Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys. Int J Radiat Biol. 1996;70(3):309-18.
14. Protection of the public in situations of prolonged radiation exposure. The application of the Commission’s system of radiological protection to controllable radiation exposure due to natural sources and long-lived radioactive residues. Ann ICRP. 1999;29(1-2):1-109.
15. Little MP, Lambert BE. Systematic review of experimental studies on the relative biological effectiveness of tritium. Radiat Environ Biophys. 2008;47(1):71-93.
16. Gueguen Y, Priest ND, Dublineau I, Bannister L, Benderitter M, Durand C, et al. In vivo animal studies help achieve international consensus on standards and guidelines for health risk estimates for chronic exposure to low levels of tritium in drinking water. Environ Mol Mutagen. 2018;59(7):586-94.
17. Ellett WH, Braby LA. The microdosimetry of 250 kVp and 65 kVp x-rays, 60Co gamma rays, and tritium beta particles. Radiat Res. 1972;51(2):229-43.
18. Tanaka K, Sawada S, Kamada N. Relative biological effectiveness and dose rate effect of tritiated water on chromosomes in human lymphocytes and bone marrow cells. Mutat Res. 1994;323(1-2):53-61.
19. Ueno AM, Furuno-Fukushi I, Matsudaira H. Induction of cell killing, micronuclei, and mutation to 6-thioguanine resistance after exposure to low-dose-rate gamma rays and tritiated water in cultured mammalian cells (L5178Y). Radiat Res. 1982;91(3):447-56.
20. Kozlowski R, Bouffler SD, Haines JW, Harrison JD, Cox R. In utero haemopoietic sensitivity to alpha, beta or X-irradiation in CBA/H mice. Int J Radiat Biol. 2001;77(7):805-15.
21. Bocian E, Ziemb-Zak B, Rosiek O, Sablinski J. Chromosome aberrations in human lymphocytes exposed to tritiated water in vitro. Curr Top Radiat Res Q. 1978;12(1-4):168-81.
22. Kamiguchi Y, Tateno H, Mikamo K. Dose-response relationship for the induction of structural chromosome aberrations in human spermatozoa after in vitro exposure to tritium beta-rays. Mutat Res. 1990;228(2):125-31.
23. Osipov AN, Grekhova A, Pustovalova M, Ozerov IV, Eremin P, Vorobyeva N, et al. Activation of homologous recombination DNA repair in human skin fibroblasts continuously exposed to X-ray radiation. Oncotarget. 2015;6(29):26876-85.
24. Tsvetkova A, Ozerov IV, Pustovalova M, Grekhova A, Eremin P, Vorobyeva N, et al. GammaH2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation. Oncotarget. 2017;8(38):64317-29.
25. Goodhead DT. Energy deposition stochastics and track structure: what about the target? Radiat Prot Dosimetry. 2006;122(1-4):3-15.
26. Goodhead DT. Fifth Warren K. Sinclair Keynote Address: Issues in quantifying the effects of low-level radiation. Health Phys. 2009;97(5):394-406.
27. Alloni D, Cutaia C, Mariotti L, Friedland W, Ottolenghi A. Modeling dose deposition and DNA damage due to low-energy beta(-) emitters. Radiat Res. 2014;182(3):322-30.
28. Chen J. Estimated yield of double-strand breaks from internal exposure to tritium. Radiat Environ Biophys. 2012;51(3):295-302.
29. Kotenko KV, Bushmanov AY, Ozerov IV, Guryev DV, Anchishkina NA, Smetanina NM, et al. Changes in the number of double-strand DNA breaks in Chinese hamster V79 cells exposed to gamma-radiation with different dose rates. Int J Mol Sci. 2013;14(7):13719-26.
30. Halazonetis TD, Gorgoulis VG, Bartek J. An oncogene-induced DNA damage model for cancer development. Science. 2008;319(5868):1352-5.
31. Moiseenko VV, Hamm RN, Waker AJ, Prestwich WV. Calculation of radiation-induced DNA damage from photons and tritium beta-particles. Part I: Model formulation and basic results. Radiat Environ Biophys. 2001;40(1):23-31.
32. Lobrich M, Shibata A, Beucher A, Fisher A, Ensminger M, Goodarzi AA, et al. gammaH2AX foci analysis for monitoring DNA double-strand break repair: strengths, limitations and optimization. Cell Cycle. 2010;9(4):662-9.
33. Saintigny Y, Roche S, Meynard D, Lopez BS. Homologous recombination is involved in the repair response of mammalian cells to low doses of tritium. Radiat Res. 2008;170(2):172-83.
34. Vorobyeva NY, Uyba V, Kochetkov OA, Astrelina TA, Pustovalova MV, Grehova AK, et al. 3H-Thymidine Influence on DNA Double Strand Breaks Induction in Cultured Human Mesenchymal Stem Cells. Medical Radiology and radiation safety. 2018;63(1):28-34. (in Russ.)
35. Vorobyeva NYu, Kochetkov OA, Pustovalova MV, Grehova AK, Blohina TM, Yashkina EI, et al. Comparative study of γH2AX foci formation in human mesenchymal stem cells exposed to 3H-thymidine, tritium oxide and X-rays. Cell Technologies in Biology and Medicine. 2018;3:205-8. (in Russ.)
36. Korzeneva IB, Kostuyk SV, Ershova LS, Osipov AN, Zhuravleva VF, Pankratova GV, et al. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium beta-radiation. Mutat Res. 2015;779:1-15.
37. Snigireva GP, Khaimovich TI, Bogomazova AN, Gorbunova IN, Nagiba VI, Nikanorova EA, et al. Cytogenetic examination of nuclear specialists exposed to chronic beta-radiation of tritium. Radiation Biol Radioecol. 2009;49(1):60-6. (in Russ.)
38. Milacic S. Changes in leukocytes caused by tritium contamination. Health Phys. 2004;86(5):457-9.
39. Flegal M, Blimkie M, Roch-Lefevre S, Gregoire E, Klokov D. The lack of cytotoxic effect and radioadaptive response in splenocytes of mice exposed to low level internal beta-particle irradiation through tritiated drinking water in vivo. Int J Mol Sci. 2013;14(12):23791-800.
40. Balakrishnan S, Rao BS. Cytogenetic Effects of Tritiated Water (HTO) in Human Peripheral Blood Lymphocytes in vitro. International Journal of Human Genetics. 2004;4(4):237-42.
41. Kiyono T. Molecular mechanisms of cellular senescence and immortalization of human cells. Expert opinion on therapeutic targets. 2007;11(12):1623-37.
42. Valentin J. Protection of the public in situations of prolonged radiation exposures : the application of the Commission’s system of radiological protection to controllable radiation exposure due to natural sources and long-lived radioactive residues. Oxford: Published for the International Commission on Radiological Protection by Pergamon, 1999; 2000.
43. Hill RL, Johnson JR. Metabolism and dosimetry of tritium. Health Phys. 1993;65(6):628-47.
44. Clement CH. Environmental protection: the concept and use of reference animals and plants. Oxford: published for the International Commission on Radiological Protection by Elsevier; 2009.
45. Icrp. Annex D. Radiation Effects in Reference Animals and Plants. Annals of the ICRP. 2008;38(4):179-229.
46. Higley KA, Kocher DC, Real AG, Chambers DB. Relative biological effectiveness and radiation weighting factors in the context of animals and plants. Ann ICRP. 2012;41(3-4):233-45.
47. Priest ND, Blimkie MS, Wyatt H, Bugden M, Bannister LA, Gueguen Y, et al. Tritium ( 3 H) Retention In Mice: Administered As HTO, DTO or as 3 H-Labeled Amino-Acids. Health Phys. 2017;112(5):439-44.
48. Muller WU, Streffer C, Molls M, Gluck L. Radiotoxicities of [3H]thymidine and of [3H]arginine compared in mouse embryos in vitro. Radiat Res. 1987;110(2):192-8.
49. Clerici L, Carroll MJ, Merlini M, Vercellini L, Campagnari F. The toxicity of tritium: the effects of tritiated amino-acids on preimplanted mouse embryos. Int J Radiat Biol Relat Stud Phys Chem Med. 1984;45(3):245-50.
50. Muller WU, Heckeley N, Streffer C. Effects of cell cycle specific exposure to 3H-thymidine or 3H-arginine on development and cell proliferation of mouse embryos. Radiat Environ Biophys. 1996;35(4):267-71.
51. Killen HM, Carroll J. The effects of tritium on embryo development: the embryotoxic effects of [3H]tryptophan. Int J Radiat Biol. 1989;56(2):139-49.