Investigation On The Correlation Between Energy Deposition And Clustered DNA Damage Induced By Low-Energy Electrons In Electromagnetic Radiation

In studies on radiation biological effects,it has been a subject to explore the correlation between radiation effects and DNA damage.This correlation can make the mechanism of the biological effects point to primary damage information.It is of essential significance to explore basic mechanisms of the biological damage induced by radiation and to establish the correlation between the final effects of radiation and the damage information at molecular level.The L-Q model suggested early on the basis of target theory gives a description that cell death or survival correlates with the double strand break of DNA induced by radiation.This model actually indicates a radiation dose associated with cell effect.The threshold model of cell response represents the correlation between radiation final effect and energy deposition in a target unit,identifyinga threshold of local energy deposition to kill cells.As presented above,these two models do not describe the correlation between biological effectiveness and the spectrum of DNA damage,and therefore they can not reveal the primary information of DNA damage resulting in radiation final effect.Due to this,to investigate the correlation between energy depositions in a target unit and the spectrum of DNA damage is a critical step for constructing the correlation between radiation biological effects and the primary spectrum of DNA damage and also is a key for explaining and understanding,theoretically,the mechanisms of radiation biological effects,thus being of scientific significance.It has been shown experimentally and theoretically that almost all types of ionizing radiation will produce abundant secondary electrons(i.e,low-energy electron of sub-keV),and these electrons will further interact with biological molecules,leading to their excitation or ionization.On the other hand,DNA,a genetic carrier,is the most critical target and lesions in DNA may bring about gene mutation,cell death,and other serious biological sequences such as cancer cell.Because of these,the DNA damage induced by low-energy electrons has been an important subject in the study of radiobiology.Knowledge of the spectrum of DNA damage is the first step not only for explaining the mechanisms of radiation effects but also for predicting radiation effects.The DNA damage induced by low-energy electrons includes single strand break(SSB),double strand break(DSB),base damage(BD),and the clustered DNA damage by combination of strand break and base damage.The clustered DNA damage,due to its high complexity,is confirmed to be of high lethal and mutagenic potential,compared to the isolated damage.Therefore,the spectrum of clustered DNA damage is of more essential significance for the radiation effects.However,by reason of the limitation of experiments and theoretical calculations,the reported studies concentrate mainly on the simple clustered DNA damage induced by particles with high primary energies and do not provide quantitative information on the different types of clustered DNA damage.This dissertation presents a systematic investigation on the clustered DNA damage induced by low-energy electrons including the dissociative electron attachment due to sub-ionization electrons as well as the correlations between the clustered DNA damage and the energy depositions in DNA target and in nucleosome target,by means of a Monte Carlo method.A more rigorous track structure model of low-energy electrons in liquid water is constructed,which accounts for the condensed-phase effect of liquid water on electron elastic scattering,the spectrums of DNA damage induced by low-energy electrons have been calculated,the contributions of sub-ionization electrons to the yields of single strand break,double strand break,and base damage of DNA have been analyzed at different primary energies of electrons,and the correlations between the different types of clustered DNA damage and the energy depositions in DNA target unit and in nucleosome target unit have been investigated.The main contents and the obtained results are summarized as follows:1.In chapter 1,the background and significance for study of the correlation between DNA damage and energy deposition are briefly introduced,and the situations and investigation methods related to this study are summarized.2.In chapter 2,two models of describing elastic scattering in liquid water,i.e.Tan model and Champion model,are presented.Tan model is based on the additivity of atom cross sections,from those of atom hydrogen and oxygen provided by the NIST database where Mott model was used,and Champion model is obtained with the use of the partial-wave formalism derived from non-relativistic wave equation of Schrodinger and especially takes into account the condensed-phase effect of liquid water.In addition,the inelastic scattering of low-energy electrons in liquid water is calculated by using the optical-data model with a D3 extension taking into account the momentum dependence of the dielectric function,and a low-energy Born correction scheme consisting of the Ochkur approximation and the classical Coulomb field correction is incorporated into this model.The optical-data model is developed by Emfietzoglou et al.on the basis of dielectric response theory.Using the track structure codes of low-energy electrons in liquid water based on the two models of calculating electron elastic scattering,respectively,together with the inelastic model due to Emfietzoglou et al.,the spatial distributions of energy deposition and inelastic scattering events of low-energy electrons with different primary energies in liquid water have been calculated and compared with other theoretical evaluations.The calculated results show that the condensed-phase effect of liquid water on electron elastic scattering is of the influence on these two distributions at lower primary energies.According to this and with the consideration that the relativistic effect is taken into account in Mott model at high energies,a more rigorous model of calculating the track structure of low-energy electrons in liquid water has been suggested.The model suggested in this chapter can provide a more exact track structure for the investigation of the DNA damage induced by low-energy electrons.3.In chapter 3,a model of simulating the spectrum of direct DNA damage induced by low-energy electrons including sub-ionization electrons has been established.Especially,in this approach the elastic interactions of low-energy electrons below 50 eV with the DNA components including four bases(adenine(A),thymine(T),guanine(G),and cytosine(C)),sugar moiety,and phosphate group are described using the cross sections calculated newly by other groups.Using the established model,base damages,DNA strand breaks,and corresponding clustered DNA damages induced by low-energy electrons including sub-ionization electrons have been systematically simulated,and the contributions of sub-ionization electrons to both base damages and DNA strand breaks have also been calculated.The following results are obtained.The contribution of sub-ionization electrons to DNA strand breaks,via dissociative electron attachment(DEA),is substantial,up to about 40-70%,but this contribution is mainly focused on SSB and they increase with increasing primary energy.The yields of complex DNA damage correlating with double strand breaks are very small,when compared to the total strand breaks.At energies of 3.0 and 4.5 keV,yields of DSB induced by sub-excitation electrons are by a factor of 230-290 smaller than corresponding yields of SSB.In addition,sub-ionization electrons contribute about 20-40%of the total base damage,the yield of damaged base pair A-T is obvious high,compared to that of damaged base pair G-C,and there is an evident correlation between SSB and damaged base pair A-T induced by sub-ionization electrons.The simulations in this chapter present the primary information of DNA damage induced by low-energy electrons,especially by sub-ionization electrons,for study of radiation biological effects and provide a basis for exploring the correlations between energy deposition and different types of clustered DNA damage.4.In chapter 4,the method of constituting the DNA target units corresponding to six types of the clustered DNA damage are proposed,and the clustered DNA damage is classified as simple and complex ones.Generally,the simple clustered DNA damage is constituted by a combination of single-strand break and the adjacent base damage,and the complex one by the double-strand break combining with the adjacent base damage.Using the Monte Carlo method,the spectrums of the clustered DNA damage induced by low-energy electrons have been systematically simulated at different primary energies,and the distribution features of the energy depositions correlating with simple and complex clustered DNA damage have also been investigated quantitatively.The present simulations show the following conclusions:(1)The relative yields of the clustered DNA damage as a function of energy deposition at different primary energies are very close to each other,the energy depositions correlating with about 90%of the total clustered DNA damage are below 150 eV,and the simple clustered DNA damage is dominant,accounting for 90%of all the clustered DNA damage.(2)The spectrums of the energy depositions correlating with the simple clustered DNA damage are in similarity for different primary energies,the energy depositions mainly distribute in the range below about 150 eV and have peaks located at about 50 eV.(3)In the range of consideraed primary energy(?4.5 keV),the obtained spectrum of SSB+BD(SSB combining with the adjacent base damage)is presented mainly by a single-strand break combining with 1 to 5 base damage,respectively.The yield of the clustered DNA damage SSB+BD is about 75-90%of the yields of all the types of the simple clustered DNA damage.The energy depositions in a target unit of SSB+BD increase with the number of base damage.There is no obvious difference between average energy depositions for a fixed complexity of SSB+BD determined by the number of base damage,indicating that the energy deposition in a target unit of SSB+BD depends on the complexity of the damage rather than the source of radiation.This is an important character for the correlation between the energy deposition and the clustered DNA damage.In addition,the SSB+BD with only one base damage is dominant,above 80%of all the SSB+BD,and the higher the complexity of SSB+BD,the larger the corresponding energy deposition.(4)In the complex clustered DNA damage,DSB+BD(DSB combining with the adjacent base damage)is of substantial contribution.At the considered primary energies,the obtained spectrum of DSB+BD is a presentation of DSB combining with 1 to 5 base damage,respectively.The DSB+BD with only one base damage contribute to about 83%of all the DSB+BD,and its average energy deposition is about 106 eV.However,it is still shown that the energy deposition increases with the complexity of DSB+BD.In spite of small yield of the complex clustered DNA damage,the biological effects resulting from them cannot be neglected.In this chapter,the correlations between the energy depositions and the clustered DNA damages with different complexities have been studied quantitatively,revealing the corresponding correlation characteristics,which construct a key link for the correlation between radiation biological effects and primary DNA damage,thus making the study of radiation biological effects point to the primary spectrums of DNA damage.5.In chapter 5,a volume model of nucleosome and the method of simulating direct DNA damage in nucleosome induced by low-energy electrons including sub-ionization electrons are established,and the concept of the DNA correlation damage is proposed.Based on the approach presented in this chapter,the spectrums of both the DNA correlation damage and the clustered DNA damage have been obtained,and the correlations between energy depositions and the DNA damage in nulceosome are quantitatively investigated.The investigations presented in this chapter give thefollowing results:(1)The relative yields of the DNA correlation damage as a function of energy deposition for different primary energies are close to each other.The energy deposition correlating with about 90%of the total DNA correlation damage is below about 180 eV.(2)SSB is dominant,accounting for 80%to 90%of all the DNA strand breaks.The spectrums of the energy depositions associated with the DNA correlation damage with SSB are in similarity for different primary energies,the energy depositions mainly distribute in the range below about 180 eV and have peaks located at about 30 eV.In addition,the SSBs without base damage and with one base damage are dominant,accounting for 70-90%and 10-20%,respectively,of all the DNA correlation damage with SSB.(3)DSB is of substantial contribution to all the DNA correlation damage with DSB.For the considered primary energies,the spectrum of the DNA correlation damage with DSB in nucleosome is presented mainly by a combination of a double-strand break and 0 to 3 base damage,respectively,and the corresponding average energy depositions are 101.86,122.79,159.80 and 229.28 eV,respectively,indicating that the more base damage combined,the higher the complexity of the damage,and the larger the energy deposition.In addition,the DNA correlation damage with DSB without base damage is dominant,accounting for about 70-80%of all the DNA correlation damage with DSB.(4)The clustered DNA damage is the DNA correlation damage with high complexity,but its yield is small,accounting for 12.48%of all the DNA correlation damage.SSB+BD is dominant in all the clustered DNA damage.The average energy depositions in a nucleosome target unit including one simple and one complex clustered DNA damage are 112.68 eV and 170.88 eV,respectively,being obviously large in contrast with that including one DNA correlation damage.The investigation on the correlation between the energy deposition in a nucleosome target unit and the spectrums of DNA damage provides a theoretical guidance for exploring the mechanisms of radiation biological effect.