| Abstract: | 在放射治療中具有高游離密度的質子治療以及重離子治療逐漸是個趨勢，現今的放射線粒子應用在臨床以及研究上的有Co-60、電子、質子、Alpha粒子 (He-4)以及重離子 (C-12、N-14、O-16、Ar-40、Fe-56)，而經放射線照射後，影響細胞存活率的因素有很多，其中線性能量轉移 (Linear Energy Transfer, LET)佔了很大的因素，本研究的目的就是模擬出這些放射線粒子隨著LET的變化對細胞DNA雙股螺旋結構所造成的傷害，並比較其生物相對效應 (relative biological effectiveness, RBE)，並結合DNA修復的情形加以探討。
本研究使用蒙地卡羅中的損傷模擬程式 (Monte Carlo Damage Simulation code, MCDS)進行模擬，此演算法可定量出放射線粒子對細胞DNA雙股螺旋結構的各種傷害，藉以探討不同的粒子對DNA傷害的複雜度，將模擬出來的結果統一與Co-60做比較，即可算出Co-60、電子、質子、He-4以及重離子 (C-12、N-14、O-16、Ar-40、Fe-56)對DNA傷害的RBE，除了探討DNA的傷害之外，本研究還針對了電子、質子與Alpha粒子，利用蒙地卡羅的切除修復程式 (Monte Carlo Excision Repair code, MCER)模擬兩種類型的DNA修復路徑：鹼基切除修復 (base excision repair, BER)與核?酸切除修復 (nucleotide excision repair, NER)，並將其數據分成四種情況，包含：正確的修復機率、變異的修復機率、無法修復的機率以及修復週期。
本研究結果顯示，在DNA傷害的結果中，隨著LET的降低，重離子造成的生物效應會比Alpha粒子還要差，而隨著LET的增加，各粒子的高複雜度DNA損傷會越來越多，此情形在重離子的部分最為突出，特別是C-12，會有這種結果是因為粒子在物質中作用速度的不同，並且隨著LET的變化而變化，而在DNA修復的結果，正確修復的機率會隨著LET的上升而下降，變異的修復機率以及無法修復的機率則會隨著LET的上升而上升，而在相同的LET下，電子的正確的修復機率低於其它粒子，而在其餘的修復機率是高於其餘粒子的。
本研究利用蒙地卡羅方法中的MCDS code對電子、質子、Alpha粒子、C-12、N-14、O-16、Ar-40以即Fe-56在不同的LET情況下進行DNA傷害的模擬，在結果中發現DNA傷害的複雜度會隨著粒子與物質作用的速度與LET的變化而有所影響，在低LET的情況下，電子的生物效應最高，而在高LET的情況下，C-12的生物效應最高，此外，LET的變化確實也會影響DNA修復，隨著放射線粒子的不同修復情況也會不一樣，雖然質子與Alpha粒子相較電子而言有著較高的游離密度，但在相同的LET下，電子的DNA修復情形最差，此結論與MCER的結果相互呼應。
Proton therapy and heavy ion therapy is very popular in recent radiotherapy. However, many kinds of radiation particles are applied in treatment and study, including Co-60, electrons, protons, He-4 (alpha particles), N-14, O-16, Ar-40, Fe-56. After exposing to radiation, the cell survival will be affected with different particles and different linear energy transfer (LET). This study simulated particles with different LET that induce the DNA damage to compare the relative biological effectiveness (RBE). Moreover, this study also simulated the outcome of the DNA repair for cells irradiated with electrons, protons and alpha particles.
In this study, we used the Monte Carlo Damage Simulation (MCDS) code to simulate the irradiated cells with various radiation particles (electrons, protons, He-4, C-12, N-14, O-16, Ar-40, Fe-56) for DNA damage induction and compared with Co-60 to calculate the RBE. Furthermore, we used Monte Carlo Excision Repair (MCER) code to simulate the probability of correct repair, mutation, conversion into double strand break (DSB) and repair recycles using repair pathway base excision repair (BER) or nucleotide excision repair (NER) for cells irradiated with electrons, protons and alpha particles.
In MCDS results, the RBE of heavy ions are lower than alpha particles when the LET is decreasing. When the LET increases, the DNA damage will be more complicated. Because different particles have different velocity in water, the LET will affect the complexity of DNA damage. In MCER results, the probability of correct repair is decreasing when the LET is increasing. However, the trends of probability of mutation and conversion into DSB are increasing as LET increases. In the same LET, the probability of correct repair of cells irradiated with electrons is lower than those of cells irradiated with protons and alpha particles. For the mutation and conversion into DSB, the probabilities of cells irradiated with electrons are higher than others cells irradiated with protons and alpha particles.
The complexity of DNA damage will be affected by LET. When the LET is low, electrons have much higher RBE than others particles. The RBE of C-12 is much higher than those RBE value of others heavy ions when the LET increases. In addition, LET is an important parameter in DNA repair. The condition of repair would be affected by LET and types of radiation particles. Although protons and alpha particles generally have higher ionization density than electrons, repair outcomes in cells irradiated with electrons repair are worse than proton and alpha particles in the same LET. |
