Irreparable DNA damage for DNA ligase IV induced by BNCT

Abstract

[Purpose] Boron neutron capture therapy (BNCT) is a system, involving the taking up of boron-10 (¹⁰B) compounds by tumour cells and irradiation with thermal neutrons. ¹⁰B absorbs a thermal neutron and yields an α(⁴He) particle and a lithium (⁷Li) nucleus, which have high linear energy transfer (LET) and path lengths. We investigated the role of non-homologous end joining (NHEJ) repair gene, Lig4 for DNA damage induced by BNCT. [Methods] We used the cultured mouse embryonic fibroblasts deficient in Lig4 and their parental cells. We examined the cell survival after neutron or γ ray irradiation by colony forming assay. Our neutron beam facility includes γ ray up to 50%. To exclude the effect of the γ ray, the pure contribution of Lig4 for repair of DNA damage by neutron-α particle reaction was examined using relative survival with various concentration of ¹⁰B at 1.5Gy. [Results] Lig4-/- cells were extremely more sensitive to neutron beam with or without ¹⁰B (10ppm) than the parental cells. In addition, relative survival showed no difference between Lig4-/- and the parental cells. [Conclusion] It is suggested that BNCT caused irreparable DNA damage by Lig4.