title: DNA damage induced by boron neutron capture therapy is partially repaired by DNA ligase IV.
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 ((10)B)-containing compound that specifically accumulates in tumor. (10)B captures neutrons and the resultant fission reaction produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). 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 (10)B-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 (10)B 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 (10)B concentration. These results indicate that BNCT-induced DNA damage is partially repaired using DNA ligase IV.
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan. nkondo@rri.kyoto-u.ac.jp.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Kondo
authors.affiliation: Division of Medical Physics, Research Reactor Institute, Kyoto University, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sakurai
authors.affiliation: Department of Neurosurgery, Osaka Medical College, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirota
authors.affiliation: Division of Medical Physics, Research Reactor Institute, Kyoto University, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Narabayashi
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kinashi
authors.affiliation: Department of Neurosurgery, Osaka Medical College, Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Miyatake
authors.affiliation: Department of Radiation Oncology, School of Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Masunaga
authors.affiliation: Department of Radiation Oncology, School of Medicine, Nara Medical University, Kashihara, Nara, 634-8522, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Ohnishi
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
mesh_terms: D000818:Animals; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects*; D002460:Cell Line; D004249:DNA Damage; D000072481:DNA Ligase ATP / Q000378:metabolism*; D004260:DNA Repair / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D013997:Time Factors
chemical_list: D000072481:DNA Ligase ATP
keywords: Boron neutron capture therapy; DNA damage; DNA ligase IV; High-LET radiation