Theoretical Study Of Direct DNA Damage Induced By Low-Energy Electrons In Electromagnetic Radiation

Biological effect of electromagnetic radiation is a subject of longstanding interest, and involved in many fields of biological research and in space science. A crucial issue in studies on radiation biological effect is to explore DNA damages induced by radiations. DNA damage can lead to cell death, gene mutation and other serious biological sequences. Therefore, the study on DNA damage is of great significance for explanations of the mechanism of radiation biological effects and for their related applications.Almost all types of ionizing radiation will produce a large number of low-energy secondary electrons in biological tissues, and these electrons interact further with biological molecules, resulting in the ionization or excitation of biological molecules. Due to these, interactions between ionizing radiations and biological materials should be extended to those of low-energy electrons with biological materials. Monte Carlo simulation is an important theoretical method for study of DNA damage induced by radiations, and it is also referred to as track structure method. At present, the researches on DNA damage by means of Monte Carlo method are focused on single-strand breaks, double-strand breaks and corresponding clustered damages induced by direct and indirect inactions of radiation. Generally, in these researches the empirical method is used to estimate base damage, and thus the base damage to adenine (A), guanine (G), thymine (T) or cytosine (C) is not taken into account directly. However, the complexity of DNA is mainly determined by base pairs A-T and G-C as well as by their arrangement sequence, and this complexity governs the genetic information in the DNA. To obtain the detailed spectrum of base damage is, therefore, of essential theoretical significance for study of DNA damage. Additionally, in almost all theoretical methods of simulating DNA damage, track interactions in water are applied to direct effects in DNA, i.e. direct energy deposition, which ignore the differences between the cross sections for the interactions of low-energy electrons with water and for the interactions of low-energy electrons with DNA bases. However, these differences are obvious according to recent theoretical studies. Especially, the recent investigations on DNA damages induced by radiations indicate that direct DNA damage, base release and DNA strand breaks, occurs well below the ionization threshold, and the mechanisms involve mainly dissociative electron attachment and possibly dissociative excitation. This mechanism of inducing DNA damage denies the traditional point of view that sub-ionization electrons can not induce the DNA damage, and is not taken into account in traditional investigations of radiation induced DNA damage. Also, this mechanism shows that for DNA strand breaks induced by such low-energy electrons, an important pathway is electrons transfer from transient base anions to the phosphate group, besides direct dissociative electron attachment, which reveals the correlation between base damage and DNA strand breaks. It is clear that this correlation is of importance for studies on the mechanisms of radiation biological effects.This dissertation has performed systematic studies for direct DNA damages induced by low-energy electrons including sub-ionization electrons by using Monte Carlo method. For theoretical consideration of simulations, a more rigorous track structure model of low-energy electrons in liquid water is constructed, DNA base damages induced by low-energy electrons are simulated with the use of ionization cross section and without traditional approximate, base release and DNA strand breaks due to sub-ionization electrons are taken into account, and the simulation method of DNA damage considering the above principles is studied. For the analyses on spectrums of DNA damages, the characteristics of the constitutions of the bases in DNA damage spectrums, the contribution of sub-ionization electrons to DNA damage, how to describe the complexity of DNA damage in terms of sub-ionization electrons and the relevance of the clustered DNA damage to its base constitution are investigated. The main contents and results are summarized as follows:1. In chapter 1, background and significance for study of DNA damage induced by low-energy electrons are briefly introduced, and the analyses on the situations concerning with this study are made.2. In chapter 2, theoretical models for interactions between low-energy electrons and water are described, and thus a method of simulating track structures of low-energy electrons in liquid water are given. This method is based on a combination of mean cross section and Mott model, resulting in an approach of calculating elastic scattering of low-energy electron in liquid water over the energy range from several eV to 10 keV. In addition, Emfietzoglou et al.'s optical data model plus the Ochkur exchange correction and the classical Coulomb-field low energy correction are used for calculating inelastic interactions of low-energy electrons with liquid water. The model presented in this chapter for simulations of low-energy electrons scattering in liquid water provides more exact track structures for the theoretical research of DNA damage induced by low-energy electrons.3. In chapter 3, Monte Carlo codes, TSLWD2 and TSLWD3 constructed on the basis of the model of describing the track structures of low-energy electrons in liquid water given in chapter 2, are systematically compared with often used codes MOCA8,KURBU and CPA100 by means of a series of the calculations, i.e. the cross sections of describing elastic and inelastic scattering of low-energy electrons in liquid water, the spacial distributions of both electron inelastic scattering events and energy depositions, absolute frequency distributions of energy depositions in target cell, and the penetration ranges of low-energy electrons in liquid water. The comparisons show that the distributions of CCPI for the five codes are close to each other when the electrons with low initial energy, but if the initial energy of electrons is higher, the CCPI calculated by code MOCA8b and KURBUC are larger than the results of code TSLWD2 and TSLWD3 evidently. Code TSLWD2,TSLWD3,MOCA8b and KURBUC give the same performance on the spacial distributions of energy deposition of inelastic scattering. The size of the target model could also affect the absolute frequency distributions of energy deposition when calculating this frequency for biological targets. The mean values for the maximum distance calculated by codes TSLED2 and TSLED3 in water for electrons with different initial energy are in good agreement. Can be seen, different cross sections and simulation models will reflect the different characteristics of the track structures, and the track structures at nanometer levels have great effect on the damages of biological macromolecules, so the comparative study in this chapter provides some reference values for the research of biological effects of ionizing radiation.4. In chapter 4, a systemic method of simulating detailed base damages is suggested. This approach includes:improvement of a volume model of DNA, generation of the DNA base sequence, conversion of ionization events in liquid water at hit site to the ionization interaction of electrons with DNA bases, and development of an algorithm to convert a base radical to a damage. Using this method, the direct DNA damages induced by low-energy electrons are systematically simulated, and DNA damage spectrums containing the detailed base damages are obtained. The yields and frequency distributions of DNA base damages, DNA strand breaks and the complicated clustered DNA damages under different relative content of base pairs for low-energy electrons with different initial energy, and the distributions of the length and number of damaged sites in DNA segments are presented. The several simulated results are compared with other experimental data or theoretical calculations. It is shown that base pair G-C is of a slightly larger probability of damage than base pair A-T, and the purine is more sensitive to 1 keV electron radiations than pyrimidine, which might be important for exploring the possible correlation between the damaged base pairs and an easy break site of the DNA strand, and that the quantity of the clustered DNA damage formed by a single strand break ssb plus damaged bases is larger than other clustered DNA damages. The relative content of base pairs A-T and G-C affects slightly the relative yields of all kinds of strand breaks and clustered DNA damages, whereas this relative content has an obvious impact on the relative yield of base damages. Most of the damaged DNA segments have a small damaged range, and they contain only 1-2 damaged sites. These results reveal the complexity and more basic characteristic of DNA damages, and provide more fundamental damage spectrum for study about the formation and classification of clustered DNA damages which may lead to serious biological consequences.5. In chapter 5, the study for DNA damages induced by radiations based on the traditional direct and indirect damage mechanisms is extended to that induced by dissociative electron attachment of sub-ionization electrons. The principles of dissociative electron attachment are described, the elastic cross sections and the cross sections of dissociative electron attachment for sub-ionization electrons interaction with DNA constitutions are given, and the method of simulating direct DNA damage induced by low-energy electrons including sub-ionization electrons are presented. Based on the approach presented in this chapter, base damages, DNA strand breaks and corresponding clustered DNA damages induced by low-energy electrons including sub-ionization electrons are systematically simulated. The contributions of sub-ionization electrons to both base damages and DNA strand breaks are calculated quantitatively, the description for the complexity of DNA damage in terms of sub-ionization electrons is given, and the characteristics of relevance of clustered DNA damage to its base constitutions are investigated. Due to the above, it is shown that the contribution of dissociative electron attachment to the yield of DNA strand breaks is about 40-70%. The yield of DNA base damages induced by dissociative electron attachment accounts for about 20-40% of the total yield, and the yields of different base damages induced by this mechanism are subject to the cross sections of dissociative electron attachment for DNA bases directly. Base pair A-T is more likely to be damaged than G-C base pair. The relative content of base pairs has little effect on the yield distributions of various strand breaks and clustered damages, but it affects the yield distributions of base damages greatly. The simulations in this chapter reveal the distribution rule of DNA clustered damages with different complexity induced by sub-ionization electrons, and reveal the related properties between DNA clustered damages and base composition, which provide deeper and more basic theory for researches of the mechanism of radiation biological effects.