No abstract available

[en] The authors are using MOCA14 track structure code of Wilson and Paretzke to generate detailed distributions of energy deposition by protons, α-particles and X-rays in cylindrical target volumes of dimensions 1-50 nm, including those corresponding to known DNA structures. Comparison of these with observed RBEs of α-particles of different energies suggests that a critical property may be deposition of threshold energy of --300 eV in a nucleosome sized target. Speculatively hypothesizing, then, that nucleosomes are the critical targets for densely ionizing radiations, leads to the conclusion that the integrity of 2-4% of the cellular genome is critical for cell survival. This interpretation may be consistent with the observed effectiveness of DNA-incorporated Iodine-125

[en] A brief outline is given of the concepts of microdosimetry and the development of the theory of dual radiation action, which was proposed as the link between the physical properties of radiation (microdosimetry) and their biological effects. A good deal of experimental evidence was consistent with the theory in its original site model form, but there were also areas of significant disagreement. More recent experiments with ultrasoft x rays and beams of correlated ions have provided critical tests which have shown that the site model does not give an adequate description of the mechanism of radiation action. A large proportion, at least, of the radiation-induced lesions are produced by highly localized energy concentrations without the need for long-range interaction of sublesions. Attempts have been made to allow for such lesions within the original postulates of the theory of dual radiation action by development of the distance model or generalized formalism using a distance-dependent interaction probability. Some of the present limitations of this approach are discussed. An alternative hypothesis, involving dose-dependent repair acting directly upon the lesions, is described. A comparison is made between consequences of these two alternative approaches. The validity of the application of microdosimetric measurements to a variety of problems is considered

[en] Unlike other DNA- and cell-damaging agents, ionizing radiations always delivers their insult in the form of discrete structured tracks. This fact has substantial implications in considering what biological effects might result at the low doses and low dose rates of main relevance in human exposures. Under the conditions of most human exposures an individual cell is unlikely to experience more than one track except over long time periods of months to years. Therefore we most need to understand the risks from these single isolated tracks. But almost all epidemiological or experimental data on radiation effects are for conditions where each cell experiences very large numbers of tracks and often in a short time period. The physical properties of radiation tracks can be determined by experimental microdosimetry at the cellular level and by Monte Carlo track-structure simulations down to the DNA and atomic levels. Such studies, in association with experimental measurements of damage to DNA and cells, can indicate the capabilities of single tracks from different radiations to cause single changes, such as mutations or stages in the progressive carcinogenic process. (author)

[en] Studies of the spatial and temporal distribution of microscopic radiation doses lead to potentially important questions regarding conventional approaches to radiation protection. The short ranges of alpha-particle and Auger-electron emissions from radionuclides lead to uncertainties in assessing their hazards. The conventional extrapolations from intermediate doses to low doses and dose rates are questioned by observed dose-rate effects in the so-called initial slope, by the total lack of data for single tracks in cells and by the possibility of multiple-cell effects. At all subcellular levels, even down to DNA, high linear-energy-transfer (LET) radiations can produce unique initial damage, different from that possible with low-LET radiations, and therefore may even, in principle, produce unique final biological effects. This questions simple extrapolations from low- to high-LET radiations and the application of universal quality factors to diverse effects. Further understanding of these questions could lead, in future, to substantial increases or decreases in estimations of risk

[en] Ionizing radiations produce many hundreds of different simple chemical products in DNA and also multitudes of possible clustered combinations. The simple products, including single-strand breaks, tend to correlate poorly with biological effectiveness. Even for initial double-strand breaks, as a broad class, there is apparently little or no increase in yield with increasing ionization density, in contrast with the large rise in relative biological effectiveness for cellular effects. Track structure analysis has revealed that clustered DNA damage of severity greater than simple double-strand breaks is likely to occur at biologically relevant frequencies with all ionizing radiations. Studies are in progress to describe in more detail the chemical nature of these clustered lesions and to consider the implications for cellular repair. (author)

[en] 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

[en] Ultrasoft X rays have provided a valuable tool to probe subcellular mechanisms of radiation actions. Sufficient data have become available to allow meaningful comparisons between laboratories and between biological assays. A brief summary is given of these data. They show that there is generally good agreement between the results from different laboratories but that there are apparently major differences in RBE between cell types which do not conform to simple expectations or explanations. This raises an intriguing conundrum which awaits satisfactory solution. The solution should provide valuable additional insight into the subcellular mechanisms, including information on spatial distributions of critical subcellular target material and/or essential difference between the responses of different cell types. A variety of potential solutions to the conundrum are discussed and it is shown how Monte Carlo track structure analyses allow some of these to be studied in terms of properties of radiation tracks over nanometre dimensions. (author)

[en] Many quantitative models have been developed for the biological effectiveness of radiation of different quality. They differ substantially in their assumptions, and a lack of firm knowledge remains as to the detailed nature of the critical early molecular damage. Analyses of microscopic features of the stochastic structures of radiation tracks have led to hypotheses on the importance of clustered damage in DNA and associated molecules. Clustered damage of greater complexity or severity is suggested to be less repairable and therefore to dominate the biological consequences. (orig.)

[en] Biophysical analyses of radiation tracks emphasize the importance of very local clustering of atomic damage within a track over microscopic distances as small as a few nanometres. They show that there must be a wide spectrum of initial physical damage within or very near to relevant macromolecules, such as DNA, and that the chemical, biochemical, repair and cellular consequences should differ considerably across this spectrum. An attempt has been made to divide this spectrum into four broad classes in order to guide development and application of assays which may better reveal the complexities and relevance of damage to DNA, and associated structures, within these classes. (author)