A theoretical model permitting estimation of yields of various DNA damages induced by radiations of varying qualities is described. It is based on the Monte-Carlo track structure simulation and DNA structure, and links physical, physicochemical and chemical stages of radiation action. Direct and indirect effects are not strictly distinguished but treated cooperatively. Good agreement between calculated and measured initial yields of double-strand breaks was observed. Other multiple and single damages of DNA are studied. When radiation quality is changed there are quantitative and qualitative transitions in the damage spectrum. The proportion of multiple damage in the damage spectrum is about 30% for low-LET radiations and increases considerably with increasing ionization density.
RADACK was conceived to simulate the radiation-induced attack to different DNA forms and complexes. It allows to separately calculate the probability of attack to each reactive atom of the sugar and of the base and takes into account the sequence-dependent structure of DNA as known from crystallographic or NMR studies or resulting from molecular modelling. The calculations are aimed to assess sequence-, structure- and ligand-dependent modulation of damages of sugar and bases, leading to single strand breaks (frank strand breaks, FSB) and alkali-labile base modifications (alkali-revealed breaks, ARB), respectively. The modelling procedure and the results of simulations for some representative structures (B, Z and quadruplex forms) are here described and discussed. The calculated relative probabilities of OH* radical attack to all reaction sites are compared to experimental FSB and ARB values. By a fitting procedure, the relative efficiencies of conversion of the C4' and C5'-centred radicals into FSB, epsilon (C4'): epsilon (C5'), and the relative efficiencies of base radicals- to- ARB conversion, epsilon(T) : epsilon(A) : epsilon(C) : epsilon(G), are then deduced for each DNA form. The ability of the model to account for the distribution of damages in DNA-ligand complexes is proven by its successful application to two DNA-protein systems : the lac repressor-lac operator complex and the nuclcosome core.
Energy deposition clusters in the nanometer scale have been investigated systematically in electron, proton, and alpha-particle tracks. The mean absolute frequency distributions of ionization clusters in nanometer sites have been computed. For locally multiply damaged sites and especially for double-strand breaks, the threshold numbers of ionizations in a site of a given diameter necessary for their induction have been estimated. At least three to six ionizations localized in sites of 1 to 4 nm diameter, respectively, are required to produce the double-strand break.
Ionizing radiations induce various damages in DNA via the hydroxyl radical OH. generated by the radiolysis of water. We compare here the radiosensitivity of B- and Z-DNA, by using a Z-prone stretch included in a plasmid. In the supercoiled plasmid, the stretch is in the Z-form, whereas it is in the B-form when the plasmid is relaxed. Frank strand breaks (FSB) and alkali-revealed breaks (ARB) were located and quantified using sequencing gel electrophoresis. We show that B- and Z-DNA have the same mean sensitivity towards radiolytic attack, for both FSB and ARB. Nevertheless, the guanine sites are more sensitive, and the cytosine sites less sensitive in Z- than in B-DNA, leading to a characteristic signature of the Z-form. The comparison of experiments with the outcome of a Monte Carlo simulation of OH. radical attack suggests that transfer of initial damage from a guanine base to its attached sugar or the adjacent 3' cytosine is more important in Z-DNA than in B-DNA.
One of the possible ways to classify track structures is application of the conventional partition techniques of analysis of multidimensional data to the track structure. Using these cluster algorithms this paper attempts to find characteristics of radiation reflecting the spatial distribution of ionizations in the primary particle track. Absolute frequency distributions of clusters giving the mean number of clusters produced by radiation per unit of deposited energy have been computed for radiation of different qualities. The results were compared with the published experimental data of cell inactivation. For particular biological objects the critical properties of radiation correlating with the cell inactivation can be found and it seems that the occurrence of a cluster of at least four ionizations formed in a domain of approximately 2-3 nm correlates with the induction of double strand break.
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