Detection of γH2AX foci in mouse normal brain and brain tumor after boron neutron capture therapy

Abstract

AimIn this study, we investigated γH2AX foci as markers of DSBs in normal brain and brain tumor tissue in mouse after BNCT. BackgroundBoron neutron capture therapy (BNCT) is a particle radiation therapy in combination of thermal neutron irradiation and boron compound that specifically accumulates in the tumor. 10B captures neutrons and produces an alpha (4He) particle and a recoiled lithium nucleus (7Li). These particles have the characteristics of extremely high linear energy transfer (LET) radiation and therefore have marked biological effects. High LET radiation causes severe DNA damage, DNA DSBs. As the high LET radiation induces complex DNA double strand breaks (DSBs), large proportions of DSBs are considered to remain unrepaired in comparison with exposure to sparsely ionizing radiation. Materials and methodsWe analyzed the number of γH2AX foci by immunohistochemistry 30min or 24h after neutron irradiation. ResultsIn both normal brain and brain tumor, γH2AX foci induced by 10B(n,α)7Li reaction remained 24h after neutron beam irradiation. In contrast, γH2AX foci produced by γ-ray irradiation at contaminated dose in BNCT disappeared 24h after irradiation in these tissues. ConclusionDSBs produced by 10B(n,α)7Li reaction are supposed to be too complex to repair for cells in normal brain and brain tumor tissue within 24h. These DSBs would be more difficult to repair than those by γ-ray. Excellent anti-tumor effect of BNCT may result from these unrepaired DSBs induced by 10B(n,α)7Li reaction.