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DNA damage induced by boron neutron capture therapy is partially repaired by DNA ligase IV

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Abstract

Boron neutron capture therapy (BNCT) is a particle radiation therapy that involves the use of a thermal or epithermal neutron beam in combination with a boron (10B)-containing compound that specifically accumulates in tumor. 10B captures neutrons and the resultant fission reaction produces an alpha (4He) particle and a recoiled lithium nucleus (7Li). These particles have the characteristics of high linear energy transfer (LET) radiation and therefore have marked biological effects. High-LET radiation is a potent inducer of DNA damage, specifically of DNA double-strand breaks (DSBs). The aim of the present study was to clarify the role of DNA ligase IV, a key player in the non-homologous end-joining repair pathway, in the repair of BNCT-induced DSBs. We analyzed the cellular sensitivity of the mouse embryonic fibroblast cell lines Lig4/p53/− and Lig4+/+ p53/− to irradiation using a thermal neutron beam in the presence or absence of 10B-para-boronophenylalanine (BPA). The Lig4/p53/− cell line had a higher sensitivity than the Lig4+/+ p53/−cell line to irradiation with the beam alone or the beam in combination with BPA. In BNCT (with BPA), both cell lines exhibited a reduction of the 50 % survival dose (D 50) by a factor of 1.4 compared with gamma-ray and neutron mixed beam (without BPA). Although it was found that 10B uptake was higher in the Lig4+/+ p53/− than in the Lig4/p53/− cell line, the latter showed higher sensitivity than the former, even when compared at an equivalent 10B concentration. These results indicate that BNCT-induced DNA damage is partially repaired using DNA ligase IV.

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Acknowledgments

This work was supported, in part, by Grants-in Aid for Scientific Research to N. Kondo (Grant No. 22890095) and to K. Ono (Grant No. 22240091) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Correspondence to Natsuko Kondo.

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The authors declare that the experiments comply with the current laws of Japan.

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The authors declare that they have no conflict of interest.

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Kondo, N., Sakurai, Y., Hirota, Y. et al. DNA damage induced by boron neutron capture therapy is partially repaired by DNA ligase IV. Radiat Environ Biophys 55, 89–94 (2016). https://doi.org/10.1007/s00411-015-0625-2

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