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

Abstract

Understanding the biological effects of neutron mixed-beam irradiation used for boron neutron capture therapy (BNCT) is important in order to improve the efficacy of the therapy and to reduce side effects. In the present study, cell viability and DNA double-strand breaks (DNA-DSBs) were examined in Chinese hamster ovary cells (CHO-K1) and their radiosensitive mutant cells (xrs5, Ku80-deficient), following neutron mixed-beam irradiation for BNCT. Cell viability was significantly impaired in the neutron irradiation groups compared to the reference gamma-ray irradiation group. The relative biological effectiveness for 10% cell survival was 3.3 and 1.2 for CHO-K1 and xrs5 cells, respectively. There were a similar number of 53BP1 foci, indicators of DNA-DSBs, in the neutron mixed-beam and the gamma-ray groups. In addition, the size of the foci did not differ between groups. However, neutron mixed-beam irradiation resulted in foci with different spatial distributions. The foci were more proximal to each other in the neutron mixed-beam groups than the gamma-ray irradiation groups. These findings suggest that neutron beams may induce another type of DNA damage, such as clustered DNA-DSBs, as has been indicated for other high-LET irradiation.

Comparative study of the effects of different radiation qualities on normal human breast cells

“…Compared to X-rays (LDR), the SF was significantly decreased after irradiation with monoenergetic neutrons (0.56 MeV, 1.2 MeV). This effectiveness of 0.56 MeV neutrons on the clonogenic survival confirms the results of Okumura et al [ 34 ]. Frankenberg-Schwager et al [ 22 ] obtained an RBE of 5.4 for a different cell line, experimental conditions and reference radiation quality.…”

DNA Double-strand Breaks Induced byFractionated Neutron Beam Irradiation for Boron Neutron Capture Therapy

“…Previously, we reported that the 53BP1 foci induced by neutron irradiation were closer to each other and had different spatial distributions from those induced by gamma rays (10). These characteristics of 53BP1 foci are indicative of clustered DNA DSBs (10,11). In this study, we found that fractionated neutron irradiation induced larger foci than did gamma irradiation.…”

Induction and disappearance of γH2AX foci and formation of micronuclei after exposure of human lymphocytes to60Co γ-rays and p(66)+ Be(40) neutrons

“…Similar findings were made by Asaithamby et al (2008) who reported lower maximum numbers of foci after exposure of human skin fibroblasts to either iron ions (150 and 236 keV/mm), silicon ions (44 keV/mm), oxygen ions (14 keV/mm) compared to g-rays. Okumura et al (2013) further detected similar numbers of p53 binding protein 1(53BP1) foci, known to colocalize with gH2AX foci (Lassmann et al 2010), after exposing hamster ovary cells to a mixed neutron beam and g-rays (i.e., RBE about 1). Importantly, to date no studies have been reported on the yield of gH2AX foci after exposure of human lymphocytes to high energy neutrons.…”

“…Therefore, it is possible that closely spaced individual foci cluster together and consequently make clear discrimination of individual foci difficult (Rübe et al 2011). Otherwise, discrimination of closely spaced and/or overlapping foci can also be limited by the optical resolution of the microscope system and lead to an underestimation of actual foci numbers (Okumura et al 2013).…”