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

Abstract

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 ( 20 Ne, 28 Si, 40 Ar, 56 Fe and 93 Nb) 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 -G 1 to mid-G 1 +3 h, henceforth called G 1 to G 1 + 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 ( D 0 :0.27 Gy) is reduced in G 1 to G 1 + 3 h by post-irradiation incubation at hypothermic temperatures and reaches a minimum ( D 0 : 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, G 1 + Sh, 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. Definitions 1. Linear energy transfer (LET ∞ ) is the energy deposited per unit length of track by an ionizing particle and usually is measured in kiloelectron volts per micrometer (in water). 2. Penumbra . Atomic interactions along the track of a heavy ion result in the ejection of electrons with energies sufficient to move beyond the region of dense ionization which constitutes the track core, and so may be considered to form a penumbra of sparsely ionizing radiations around the track core. 3. RBE . The effectiveness of a densely ionizing radiation (heavy ion) compared to a sparsely ionizing radiation, e. g. X- or γ -photons, is measured by the inverse ratio of the doses of each radiation needed to produce a given radiobiological effect, and is known as the relative biological effectiveness (RBE): the usual reference radiation is 250 kVp X-rays. 4. D 0 is a measure of the radiosensitivity of a cell as determined from the (limiting) linear slope of the survival curve, and is the dose in Gray (1 Gy ≡ 1 Joule kg -1 ) required to reduce the survival at a point anywhere in that region of the survival curve to 37% of its value at that point.

Tumor therapy and track structure

“…This was shown in the comparison of ataxia (AT) cells with normal cells [17], in the behavior of a temperature-sensitive mutant [18], and in the behavior of repair-deficient mutants of Chinese hamster ovary (CHO) cells [19]. In all cases, the RBE maximum disappears when repair is turned off, and the x-ray dose-effect curve becomes purely exponential.…”