Responses of synchronous L5178Y S/S cells to heavy ions and their significance for radiobiological theory

Synchronous suspensions of the radiosensitive S/S variant of the L5178Y murine leukaemic lymphoblast at different positions in the cell cycle were exposed aerobically to segments of heavy-ion beams (²⁰Ne, ²⁸Si, ⁴⁰Ar, ⁵⁶Fe and ⁹³Nb) in the Bragg plateau regions of energy deposition. The incident energies of the ion beams were in the range of 460 ± 95 MeV u^-1, and the calculated values of linear energy transfer (LET∞) for the primary nuclei in the irradiated samples were 33 ± 3, 60 ± 3, 95 ± 5, 213 ± 21 and 478 ± 36 keV μm^-1, respectively; 280 kVp X-rays were used as the baseline radiation. Generally, the maxima or inflections in relations between relative biological effectiveness (RBE) and LET∞ were dependent upon the cycle position at which the cells were irradiated. Certain of those relations were influenced by post-irradiation hypothermia. Irradiation in the cell cycle at mid-G₁ to mid-G₁ + 3 h, henceforth called G₁ to G₁ + 3 h, resulted in survival curves that were close approximations to simple exponential functions. As the LET∞ was increased, the RBE did not exceed 1.0, and by 478 keV μm^-1 it had fallen to 0.39. Although similar behaviour has been reported for inactivation of proteins and certain viruses by ionizing radiations, so far the response of the S/S variant is unique for mammalian cells. The slope of the survival curve for X-photons (D₀: 0.27 Gy) is reduced in G₁ to G₁ + 3 h by post-irradiation incubation at hypothermic temperatures and reaches a minimum (D₀: 0.51 Gy) at 25°C. As the LET∞ was increased, however, the extent of hypothermic recovery was reduced progressively and essentially was eliminated at 478 keV μm^-1. At the cycle position where the peak of radioresistance to X-photons occurs for S/S cells, G₁ + 8 h, increases in LET∞ elicited only small increases in RBE (at 10% survival), until a maximum was reached around 200 keV μm^-1. At 478 keV μm^-1, what little remained of the variation in response through the cell cycle could be attributed to secondary radiations (δ rays) and smaller nuclei produced by fragmentation of the primary ions.