Radiation research. Supplement最新文献

In the past cellular fast-mixing techniques have been used to investigate the time resolution of radiation processes that lead to modification of radiation response in bacterial and mammalian cellular systems. So far, published studies have been confined to effects with low-LET electron beams. The brief for this paper was to discuss where, and under what conditions, such a technique could be used to advantage with high-LET particle beams. Criteria for the experimental design, including conditions of flow rate, dose rate, and mixing times, are discussed. Radiobiological problems appropriate for applications of fast-particle beams are also discussed. These include studies to reveal possible multicomponents in cellular sensitization by oxygen and electron-affinic radiation sensitizers, studies designed to assist in the resolution of direct and indirect effects, and resolution of intracellular DNA damage.

There are two facilities for clinical trials with protons in Japan: the National Institute of Radiological Sciences (NIRS), Chiba, and the Particle Radiation Medical Science Center (PARMS), University of Tsukuba. At the National Institute of Radiological Sciences, patient treatment with the 70 MeV proton beam began in November 1979, and 29 patients were treated through December 1984. Of 11 patients who received protons only, 9 have had local control of the tumor. Two of the 9 patients, suffering from recurrent tumor after radical photon beam irradiation, developed complications after proton treatment. In the patients treated with photons or neutrons followed by proton boost, tumors were controlled in 12 of 18 patients (66.6%), and no complications were observed in this series. Malignant melanoma could not be controlled with the proton beam. A spot-beam-scanning system for protons has been effectively used in the clinical trials to minimize the dose to the normal tissues and to concentrate the dose in the target volume. At the Particle Radiation Medical Science Center, University of Tsukuba, treatment with a vertical 250 MeV proton beam was begun in April 1983, and 22 patients were treated through February 1984. Local control of the tumor was observed in 14 of 22 patients (63.6%), whereas there was no local control in the treatment of glioblastoma multiforme. There have been no severe complications in patients treated at PARMS. The results suggest that local control of tumors will be better with proton beams than with photon beams, whereas additional modalities are required to manage radioresistant tumors.

Patient treatments at TRIUMF (Tri-University Meson Facility, Vancouver, B. C.) use a moving spot raster scan technique where the pion range is modulated in depth for each position of the moving spot. The spot scans in a stepwise fashion and can produce any desired field shape. This approach provides very good dose uniformity across the treatment field and allows maximum flexibility in shaping the treatment volume. Survival of cultured cells has been used as a biological dosimeter to test the isoeffectiveness of the pion dose distributions, which must be shaped in depth to compensate for the depth-dependent LET distribution. Isoeffectiveness across the treatment field has also been verified using this system, which involves irradiating cells supported in a gelatin matrix. The response of pig skin to pion irradiation at TRIUMF has provided a check on the in vivo RBE for acute effects derived from our earlier studies with mouse foot. In addition, the pig skin reactions have been followed for several months to assess the later dermal response. The RBE of our pion beam relative to 270 kVp X rays is approximately 1.5 for both the acute epidermal and the later dermal responses.

Most quantitative models of radiation action in mammalian cells make the implicit assumption that all relevant repair processes proceed in a dose-independent manner. Thus it is implicitly assumed that the repair processes (1) follow totally unsaturated kinetics, (2) are not themselves inactivated by the radiation, and (3) are not enhanced by the presence of radiation damage. Contradiction of any of these three assumptions could have important theoretical and practical implications. The possible relevance of (1) and (2) in mammalian cells is discussed by considering a selection of saturable repair (and related) models. Repair inactivation is improbable, but repair saturation provides a ready explanation of common radiobiological phenomena without the need for the existence of "sublethal" damage. Furthermore, such models can "explain" additional phenomena which appear as contradictions to some sublethal damage models. Recent experiments by Wheeler and Wierowski have demonstrated the existence of dose-dependent repair of DNA damage in mammalian cells.

Ionizing radiation produces a range of damage types in cellular DNA. All damage types do not have the same biological significance. Here arguments are presented supporting the view that lesions in which damage is present on both strands in a local region of the DNA (locally multiply damaged sites--LMDS) will present problems for cellular repair processes. We have previously shown that lesions produced in DNA by individual OH radicals, i.e., single OH species acting alone, are ineffective in mammalian cell killing [J.F. Ward, W.F. Blakely, and E.I. Joner, Radiat. Res. 103, 383-392 (1985)]. We have similar evidence in mutagenesis studies (Ward and Calabro-Jones, unpublished data). Thus the formation of such damage by individual OH radicals formed by ionizing radiation would be similarly ineffectual. Earlier [J.F. Ward, Radiat. Res. 86, 185-195 (1981)] we suggested that OH-radical scavenging studies were consistent with the scavenging of OH radicals in volumes of high radical density, spurs, etc., i.e., in volumes which, when they overlap the DNA, will cause the production of LMDS. The individual constituent lesions of LMDS will be formed as a result of direct ionization or as a result of an OH-radical attack. Both mechanisms can lead to base damage or strand breakage. It is clear that damage in both bases of a deoxyribonucleotide pair leads to loss of base sequence information and can be repaired correctly only by accident or in a recombinational process.(ABSTRACT TRUNCATED AT 250 WORDS)