The effectiveness of the high-LET radiations from the boron neutron capture [¹⁰B(n,α)⁷Li] reaction determined for induction of chromosome aberrations and apoptosis in lymphocytes of human blood samples

Abstract

Provided that a selective accumulation of ¹⁰B-containing compounds is introduced in tumor cells, following irradiation by thermal neutrons produces high-LET alpha-particles (⁴He) and recoiling lithium-7 (⁷Li) nuclei emitted during the capture of thermalized neutrons (0.025 eV) from ¹⁰B. To estimate the biological effectiveness of this boron neutron capture [¹⁰B(n,α)⁷Li] reaction, the chromosome aberration assay and the flow cytometry apoptosis assay were applied. At the presence of the clinically used compounds BSH (sodium borocaptate) and BPA (p-boronophenylalanine), human lymphocytes were irradiated by sub-thermal neutrons. For analyzing chromosome aberrations, human lymphocytes were exposed to thermally equivalent neutron fluences of 1.82 × 10¹¹ cm⁻² or 7.30 × 10¹¹ cm⁻² (corresponding to thermal neutron doses of 0.062 and 0.248 Gy, respectively) in the presence of 0, 10, 20, and 30 ppm of BSH or BPA. Since the kerma coefficient of blood increased by 0.864 × 10⁻¹² Gy cm² per 10 ppm of ¹⁰B, the kerma coefficients in blood increase from 0.34 × 10⁻¹² cm² (blood without BSH or BPA) up to 2.93 × 10⁻¹² Gy cm² in the presence of 30 ppm of ¹⁰B. For the ¹⁰B(n, α)⁷Li reaction, linear dose–response relations for dicentrics with coefficients α = 0.0546 ± 0.0081 Gy⁻¹ for BSH and α = 0.0654 ± 0.0075 Gy⁻¹ for BPA were obtained at 0.062 Gy as well as α = 0.0985 ± 0.0284 Gy⁻¹ for BSH and α = 0.1293 ± 0.0419 Gy⁻¹ for BPA at 0.248 Gy. At both doses, the corresponding ¹⁰B(n, α)⁷Li reactions from BSH and BPA are not significantly different. A linear dose–response relation for dicentrics also was obtained for the induction of apoptosis by the ¹⁰B(n, α)⁷Li reaction at 0.248 Gy. The linear coefficients α = 0.0249 ± 0.0119 Gy⁻¹ for BSH and α = 0.0334 ± 0.0064 Gy⁻¹ for BPA are not significantly different. Independently of the applied thermal neutron doses of 0.062 Gy or 0.248 Gy, the ¹⁰B(n, α)⁷Li reaction from 30 ppm BSH or BPA induced an apparent RBE of about 2.2 for the production of dicentrics as compared to exposure to thermal neutrons alone. Since the apparent RBE value is defined as the product of the RBE of a thermal neutron dose alone times a boron localization factor which depends on the concentration of a ¹⁰B-containing compound, this localization factor determines the biological effectiveness of the ¹⁰B(n, α)⁷Li reaction.