Interaction between the biological effects of high- and low-LET radiation dose components in a mixed field exposure

Abstract Purpose: The relative biological effectiveness of two epithermal neutron sources, a reactor based source at Studsvik, Sweden, and a proton accelerator-based source in Birmingham, UK, was studied in relation to the proportional absorbed dose distribution as a function of neutron energy. Evidence for any interactions between the effects of biological damage induced by high- and low-linear energy transfer (LET) dose components, in this ‘mixed field’ irradiation, was also examined Materials and methods: Clonogenic survival in Chinese Hamster-derived V79 cells was used to assess biological effectiveness in this study. Cells were irradiated in suspension at 4°C at depths of 20, 35, 50 and 65 mm in a water phantom. This prevented the repair of sublethal damage, predominantly that produced by both incident and induced γ-rays in the field, over the variable periods of exposure required to irradiate cells with the same total absorbed dose. Cell survival, as a function of the absorbed radiation dose and depth in the phantom, was compared with Monte Carlo N-Particle (MCNP) calculations of the proportional absorbed dose distribution as a function of neutron energy for the two sources. Results: In terms of the dose-related reduction in clonogenic cell survival, the epithermal neutron source at Studsvik was more biologically effective than the Birmingham source at all depths considered in the phantom. Although the contribution from the high-LET dose component was greater for the Studsvik source at 20 mm depth in the phantom, at greater depths the dose contribution from the high-LET dose component at Studsvik overlap with those for the Birmingham source. However, the most striking difference is in the fast neutron component to the dose of the two sources, neutron energies > 1 MeV were only associated with the Studsvik source. The relative biological effectiveness (RBE) of both sources declined slightly with depth in the phantom, as the total high-LET dose component declined. The maximum source RBE for Studsvik was 2.70 ± 0.50 at 20 mm; reduced to 2.10 ± 0.35 at depths of 50 and 65 mm. The corresponding values for Birmingham were 1.68 ± 0.25 and 1.31 ± 0.19, all values relate only to the surviving fraction of V79 cells at 37%, since RBE values are only applicable to the selected endpoint. Based on a dose reduction factor (DRF) of 1.0 for the total low-LET component to the absorbed dose, the RBE values for the high-LET dose component (fast neutrons and induced protons from the nitrogen capture reaction) was 14.5 and 7.05 for the Studsvik and Birmingham neutron sources, respectively. This is well outside the range of RBE historically reported values for V79 cells for the same level of cell survival for fast neutrons. The calculation of RBE values, based on the proportional absorbed dose distribution as a function of neutron energy, from historical data, and using a RBE of 1.8 for the dose from the nitrogen capture reaction, suggests RBE values for the total high-LET dose component of 3.1–2.8 and 2.5–2.0 for Studsvik and Birmingham, respectively, values again declining with depth in the phantom. Conclusions: The overall biological effectiveness of the mixed field irradiation from an epithermal neutron sources depends on the composition and quality of the different dose components. The experimentally derived RBE values for the total high-LET dose components in these ‘mixed field’ irradiations are well in excess of historical data for fast neutrons. The difference between the historically expected and the observed RBE values is attributed to the interactions between the damage produced by high- and low-LET radiation.