The role of repair in the survival of mammalian cells from heavy ion irradiation: Approximation to the ideal case of target theory

Lett, J. T.; Cox, A.B.; Story, Michael D.

doi:10.1016/0273-1177(89)90427-4

Cited by 6 publications

(3 citation statements)

References 15 publications

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“…Such large cross-sections have not been observed experimentally for V79 cells, but there are several more sensitive cell lines where values exceeding the geometrical limit have been observed. Examples include human lymphocytes [47] and the repair-deficient LS1784 S/S cells [48]. For small impact parameters the model of Eq.…”

Section: Amorphous Track Models Of Radiation Actionmentioning

confidence: 99%

Applications of amorphous track models in radiation biology

Cucinotta

Nikjoo

Goodhead

1999

Radiation and Environmental Biophysics

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The average or amorphous track model uses the response of a system to gamma-rays and the radial distribution of dose about an ion's path to describe survival and other cellular endpoints from proton, heavy ion, and neutron irradiation. This model has been used for over 30 years to successfully fit many radiobiology data sets. We review several extensions of this approach that address objections to the original model, and consider applications of interest in radiobiology and space radiation risk assessment. In the light of present views of important cellular targets, the role of target size as manifested through the relative contributions from ion-kill (intra-track) and gamma-kill (inter-track) remains a critical question in understanding the success of the amorphous track model. Several variations of the amorphous model are discussed, including ones that consider the radial distribution of event-sizes rather than average electron dose, damage clusters rather than multiple targets, and a role for repair or damage processing.

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Section: Amorphous Track Models Of Radiation Actionmentioning

confidence: 99%

Applications of amorphous track models in radiation biology

Cucinotta

Nikjoo

Goodhead

1999

Radiation and Environmental Biophysics

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“…Rigorous calculations of inactivation cross sections for radiation targets are possible only when the radiation damage is not modified by post-irradiation metabolic processes (Lea 1955;Todd & Tobias 1974;Zimmer 1981), circumstances that usually do not apply to cells. That ideal case (Zimmer 1981) can be approached, however, if cellular repair systems are rendered ineffective or inoperative (Lett et al 1989), which happened when the L5178Y S/S variant was exposed to 93Nb ions at an letx of 478 keV pm-1 during the early part of the cell cycle (Gx to Gj + 3 h). Apart from penumbral effects, etc., all the requirements of simple target theory were met.…”

Section: Conclusio N Smentioning

confidence: 99%

“…Of more general importance is the principle that radiobiological phenomena can be explained properly neither by the tenets of radiation physics alone nor by the addition of a simple, LET^-dependent, parameter, the so-called quality factor, which must encompass every biological factor involved in the responses of all animate systems to radiation to a given quality (Lett 1987;Lett et al 19866). One medical consequence of this principle actually involves the environmental exposure of astronauts to heavy ions during future manned space flights of long duration beyond the earth's magnetosphere (Lett et al 1989). Radiation hazards from such flights for humans will include the effects of prolonged chronic exposure to the spectrum of galactic heavy ions that pervades deep space, and of which the flux of 56Fe ions is probably the most dangerous component (Silberberg et al 1984).…”

Section: We Are Indebted To Drmentioning

confidence: 99%

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

Lett

Cox

Story

et al. 1989

Proc. R. Soc. Lond. B

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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.

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