Abstract
BackgroundBoron neutron capture reaction (BNCR) is based on irradiation of tumors after accumulation of boron compound. 10B captures neutrons and produces an alpha (4He) particle and a recoiled lithium nucleus (7Li). These particles have the characteristics of high linear energy transfer (LET) radiation and have marked biological effects. The purpose of this study is to verify that BNCR will increase cell killing and slow disappearance of repair protein-related foci to a greater extent in DNA repair-deficient cells than in wild-type cells.MethodsChinese hamster ovary (CHO-K1) cells and a DNA double-strand break (DSB) repair deficient mutant derivative, xrs-5 (Ku80 deficient CHO mutant cells), were irradiated by thermal neutrons. The quantity of DNA-DSBs following BNCR was evaluated by measuring the phosphorylation of histone protein H2AX (gamma-H2AX) and 53BP1 foci using immunofluorescence intensity.ResultsTwo hours after neutron irradiation, the number of gamma-H2AX and 53BP1 foci in the CHO-K1 cells was decreased to 36.5-42.8% of the levels seen 30 min after irradiation. In contrast, two hours after irradiation, foci levels in the xrs-5 cells were 58.4-69.5% of those observed 30 min after irradiation. The number of gamma-H2AX foci in xrs-5 cells at 60-120 min after BNCT correlated with the cell killing effect of BNCR. However, in CHO-K1 cells, the RBE (relative biological effectiveness) estimated by the number of foci following BNCR was increased depending on the repair time and was not always correlated with the RBE of cytotoxicity.ConclusionMutant xrs-5 cells show extreme sensitivity to ionizing radiation, because xrs-5 cells lack functional Ku-protein. Our results suggest that the DNA-DSBs induced by BNCR were not well repaired in the Ku80 deficient cells. The RBE following BNCR of radio-sensitive mutant cells was not increased but was lower than that of radio-resistant cells. These results suggest that gamma-ray resistant cells have an advantage over gamma-ray sensitive cells in BNCR.
Highlights
Boron neutron capture reaction (BNCR) is based on irradiation of tumors after accumulation of boron compound. 10B captures neutrons and produces an alpha (4He) particle and a recoiled lithium nucleus (7Li)
We report here that the amount of DNA damage induced by BNCR is significantly greater in D-NHEJdefective cells compared with wild-type CHO-K1 cells, suggesting that a deficiency in the repair of double-strand break (DSB) contributes to the enhanced sensitivity of D-NHEJdefective cells to BNCR
These results indicate that the xrs-5 cells have not repaired their DNA-DSBs 2 hours after BNCR
Summary
Boron neutron capture reaction (BNCR) is based on irradiation of tumors after accumulation of boron compound. 10B captures neutrons and produces an alpha (4He) particle and a recoiled lithium nucleus (7Li). The principle underlying the Boron Neutron Capture Reaction (BNCR) is that tumor cells containing 10B can be destroyed efficiently by the 10B(n,a)7Li fission reaction through the delivery of effective thermal neutron doses at the target depth During this reaction, an alpha particle and a recoiling 7Li ion with an average total kinetic energy of 2.34 MeV are released when compounds containing 10B that have accumulated in the tumor cells are exposed to thermal neutrons. An alpha particle and a recoiling 7Li ion with an average total kinetic energy of 2.34 MeV are released when compounds containing 10B that have accumulated in the tumor cells are exposed to thermal neutrons These particles have the characteristics of high linear energy transfer (LET) radiation and produce enhanced biological effects. It is generally accepted that high LET radiation induces more DNA-DSBs than low LET radiation
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