Impact of neutron radiation on the viability of tumor cells cultured in the presence of boron-10 isotope
https://doi.org/10.20862/0042-4676-2016-97-5-283-288
Abstract
Objective: to investigate the impact of a neutron beam formed with the accelerator-based epithermal neutron source designed at the G.I. Budker Institute of Nuclear Physics (INP) on the viability of human and animal tumor cells cultured in the presence of boron-10 isotope.
Material and methods. Human U251 and T98G glioma cells and Chinese hamster CHO-K1 and V-79 cells were incubated at various concentrations in the culture medium containing 10B-enriched L-boronophenylalanine. The cells were irradiated with a neuron beam using the accelerator-based epithermal neuron source. A clonogenic assay was used to evaluate the viability of the irradiated cells. The absorbed doses obtained from elastic scattering of fast neutrons by substance nuclei and the doses obtained from boron neutron capture were calculated using the NMS code. The absorbed doses of gamma-radiation were measured with a mixed radiation dosimeter.
Results. The viability of boron-containing and intact human U251 and T98G cell lines and Chinese hamster CHO-K1 and V-79 cells was analyzed after neutron beam radiation. Irradiation of all four cell lines were cultured in the presence of 10B was shown to reduce their colony-forming capacity compared with the control. Elevated boron levels in the culture medium resulted in a significant decrease in the proportion of survived cells. Radiation had the most pronounced impact on the proliferative capacity of the human U251 glioma cell lines.
Conclusion. The cultures of human tumor cells and mammalian cells demonstrated that the neutron beam formed with the accelerator-based epithermal neutron source designed at the INP, was effective in reducing the viability of tumor cells in the presence of 10B
About the Authors
O. Yu. VolkovaRussian Federation
PhD in Biol. Sci., Senior Research Associate
L. V. Mechetina
Russian Federation
PhD in Biol. Sci., Senior Research Associate
A. V. Taranin
Russian Federation
Dr. of Biol., Head of the Laboratory
A. A. Zaboronok
Japan
MD, PhD, Associate Professor
K. Nakai
Japan
MD, PhD, DSc, Associate Professor
S. I. Lezhnin
Russian Federation
S. A. Frolov
Russian Federation
Engineer
D. A. Kasatov
Russian Federation
Junior Research Associate
A. N. Makarov
Russian Federation
PhD in Phys. and Math. Sci., Junior Research Associate
I. N. Sorokin
Russian Federation
PhD in Tech. Sci., Research Associate
T. V. Sycheva
Russian Federation
Engineer
I. M. Shchudlo
Russian Federation
Postgraduate
S. Yu. Taskaev
Russian Federation
Dr of Phys. and Math., Leading Research Associate
References
1. Locher G.L. Biological effects and therapeutic possibilities of neutrons. Am. J. Roentgenol. Radium Ther. 1936; 36: 1–13.
2. Sauerwein W., Wittig A., Moss R., Nakagawa Y. (eds). Neutron capture therapy: pronciples and applications. Springer; 2012.
3. Tsuchida K., Kiyanagi Y., Uritani A., Watanabe K., Shimizu H., Hirota K. et al. Development of an accelerator-driven compact neutron source for BNCT in Nagoya University. In: Book of abstracts of the 16 International Congress on Neutron Capture Therapy. 2014, June 14–19; Helsinki, Finland: 206–7.
4. Kumada H., Kurihara H., Yoshioka M., Kobayashi H., Matsumoto H., Sugano T. et al. Development of beryllium-based neutron target system with three-layer structure for accelerator-based neutron source for boron neutron capture therapy. Appl. Radiat. Isot. 2015; 106: 78–83.
5. Abe Y., Fuse M., Fujii R., Nakamura M., Imahoru Y., Itami J. Hospitalbased boron neutron capture therapy in National Cancer Center. An installation design for the accelerator-based epithermal neutron source. In: Abstracts of 15th International Congress on Neutron Capture Therapy. 2012, Sept. 10–14; Tsukuba, Japan: 109–10.
6. Таскаев С.Ю. Ускорительный источник эпитепловых нейтронов. Физика элементарных частиц и атомного ядра. 2015; 46 (6): 1770–830. [Taskaev S.Yu. Accelerator based epithermal neutron source. Fizika Elementarnykh Chastits i Atomnogo Yadra (Physics of Elementary Particles and Atomic Nuclei, Russian journal). 2015; 46 (6): 1770–830 (in Russ.).]
7. Wittig A., Huiskamp R., Moss R., Bet P., Kriegeskotte C., Scherag A. et al. Biodistribution of (10)B for Boron Neutron Capture Therapy (BNCT) in a mouse model after injection of sodium mercaptoundecahydro-closo-dodecaborate and l-para-boronophenylalanine. Radiat. Res. 2009; 172 (4): 493–9.
8. Wittig A., Moss R., Sauerwein W. Glioblastoma, brain metastases and soft tissue sarcoma of extremities: candidate tumors for BNCT. Appl. Radiat. Isot. 2014; 88: 46–9.
9. Sun T., Zhou Y., Xie X., Chen G., Li B., Wei Y. et al. Selective uptake of boronophenylalanine by glioma stem/progenitorcells. Appl. Radiat. Isot. 2012; 70 (8): 1512–8.
10. Wittig A., Sauerwein W., Coderre J. Mechanisms of transport of p-borono-phenylalanine through the cell membrane in vitro. Radiat. Res. 2000; 153 (2): 173–80.
11. Yasui L., Kroc T., Gladden S., Andorf C., Bux S., Hosmane N. Boron neutron capture in prostate cancer cells. Appl. Radiat. Isot. 2012; 70 (1): 6–12.
12. Yamamoto T., Nakai K., Kageji T., Kumada H., Endo K., Matsuda M. et al. Boron neutron capture therapy for newly diagnosed glioblastoma. Radiother. Oncol. 2009; 91 (1): 80–4.
13. Kankaanranta L., Seppala T., Koivunoro H., Valimaki P., Beule A., Collan J. et al. L-boronophenylalanine-mediated boron neutron capture therapy for malignant glioma progressing after external beam radiation therapy: a Phase I study. Int. J. Radiat. Oncol. Biol. Phys. 2011; 80 (2): 369–76.
14. Wadabayashi N., Honda C., Mishima Y., Ichihashi M. Selective boron accumulation in human ocular melanoma vs surrounding eye components after 10B1-p-boronophenylalanine administration. Prerequisite for clinical trial of neutron-capture therapy. Melanoma Res. 1994; 4 (3): 185–90.
15. Yoshino K., Suzuki A., Kakihana H., Honda C., Mishima Y., Kobayashi T. et al. Improvement of solubility of p-boronophenylalanine by complex formation with monosaccharides. Strahlenther. Onkol. 1989; 165 (2–3): 127–9.
16. Иванов А.А., Касатов Д.А., Кошкарев А.М., Макаров А.Н., Остреинов Ю.М., Сорокин И.Н. и др. Получение протонного пучка с током 5 мА в ускорителе-тандеме с вакуумной изоляцией. Письма в Журнал технической физики. 2016; 42 (12): 1–8. [Ivanov A.A., Kasatov D.A., Koshkarev A.M., Makarov A.N., Ostreinov Yu.M., Sorokin I.N. et al. Generation of the proton beam of 5 mA on a tandem accelerator with vacuum insulation. Pis'ma v Zhurnal Tekhnicheskoy Fiziki (Technical Physics Letters, Russian journal). 2016; 42 (12): 1–8 (in Russ.).]
17. Bayanov B., Kashaeva E., Makarov A., Malyshkin G., Samarin S., Taskaev S. A neutron producing target for BINP accelerator-based neutron source. Appl. Radiat. Isot. 2009; 67 (7–8): 282–4.
18. Yurov D., Anikeev A., Bagryan- sky P., Brednikhin S., Frolov S., Lezhnin S. et al. Parameters optimization in a hybrid system with a gas dynamic trap based neutron source. Fusion Eng. Des. 2012; 87 (9): 1684–92.
19. Санников А.В., Лебедев В.Н., Кустарев В.Н., Савицкая Е.Н., Спиров Е.Г. Индивидуальный дозиметр смешанного излучения ДВГН-01: Разработка и исследование характеристик. Препринт ИФВЭ 2005-6. Протвино; 2005. [Sannikov A.V., Lebedev V.N., Kustarev V.N., Savitskaya E.N., Spirov E.G. The individual dosimeter of mixed radiation DVGN-01: development and study of characteristics. IHEP Preprint 2005-6. Protvino; 2005 (in Russ.).]
20. Franken N., Rodermond H., Stap J., Haveman J., Bree C. Clonogenic assay of cells in vitro. Nat. Protoc. 2006; 1 (5): 2315–9.
21. Yoshida F., Matsumura A., Shibata Y., Yamamoto T., Nakauchi H., Okumura M. et al. Cell cycle dependence of boron uptake from two boron compounds used for clinical neutron capture therapy. Cancer Lett. 2002; 187 (1–2): 135–41.
22. Sato E., Yamamoto T., Shikano N., Ogura M., Nakai K., Yoshida F. et al. Intracellular boron accumulation in CHO-K1 cells using amino acid transport control. Appl. Radiat. Isot. 2014; 88: 99–103.
23. Yoshida F., Yamamoto T., Nakai K., Zaboronok A., Matsumura A. Additive effect of BPA and GdDTPA for application in accelerator-based neutron source. Appl. Radiat. Isot. 2015; 106: 247–50.
24. Van Meir E.G., Hadjipanayis C.G., Norden A.D., Shu H.K., Wen P.Y., Olson J.J. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. Cancer J. Clin. 2010; 60 (3): 166–93.
25. Okumura K., Kinashi Y., Kubota Y., Kitajima E., Okayasu R., Ono K. et al. Relative biological effects of neutron mixed-beam irradiation for boron neutron capture therapy on cell survival and DNA double-strand breaks in cultured mammalian cells. J. Radiat. Res. 2013; 54 (1): 70–5.
26. Kinashi Y., Takahashi S., Kashino G., Okayasu R., Masunaga S., Suzuki M. et al. DNA doublestrand break induction in Ku80-deficient CHO cells following Boron Neutron Capture Reaction. Radiat. Oncol. 2011; 5 (6): 106.
27. Wang P., Zhen H., Jiang X., Zhang W., Cheng X., Guo G. et al. Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax. BMC Cancer. 2010; 2 (10): 661.
Review
For citations:
Volkova O.Yu., Mechetina L.V., Taranin A.V., Zaboronok A.A., Nakai K., Lezhnin S.I., Frolov S.A., Kasatov D.A., Makarov A.N., Sorokin I.N., Sycheva T.V., Shchudlo I.M., Taskaev S.Yu. Impact of neutron radiation on the viability of tumor cells cultured in the presence of boron-10 isotope. Journal of radiology and nuclear medicine. 2016;97(5):283-288. (In Russ.) https://doi.org/10.20862/0042-4676-2016-97-5-283-288