透過您的圖書館登入
IP:3.147.59.29
  • 學位論文

62 MeV質子在不同深度所造成之DNA損傷及修復之研究

DNA damage induction and repair of cells irradiated by 62 MeV proton beams at different depths

指導教授 : 蕭雅云

摘要


質子治療在物理上具有劑量集中的特性,質子在進入人體後,劑量沉積會隨著深度而緩慢增加,在靠近粒子範圍尾端會達到一高峰值,稱之為Bragg peak(布拉格峰)。因此在尚未到達治療目標前,沿途的組織仍有接受到質子束的影響。透過此研究觀察在不同深度,質子所造成之單位劑量下的DNA損傷及修復情形。另外,也將比較不同深度的RBE值變化和探討其與LET之關係。 在本篇研究,透過蒙地卡羅方法(Monte Carlo damage simulation, MCDS 和Monte Carlo excision repair, MCER)進行電腦模擬,觀察62 MeV的單能質子及SOBP質子在不同深度對細胞DNA造成之損傷和修復。 根據MCDS模擬結果,隨著深度增加,DNA總損傷量下降了0.7% - 17.09%,而DSB誘導量上升了3.44% - 80.8%,相較於表面深度,Bragg peak深度的DSB誘導量約莫增加了1.5 - 1.8倍。另外透過MCER模擬,結果顯示隨著深度增加,錯誤修復與DSB轉換的機率會隨之上升,且正確修復的機率會隨之降低。透過DSB轉換量和誘導量所計算出的RBE值皆會隨著深度增加而提升,並且皆與LET呈高度線性關係,R平方值約為0.99。 隨著深度越接近布拉格峰深度,總損傷量雖然會隨之下降,但DSB量(包含DSB誘導量和轉換量)卻會隨之上升,此外,RBE值除了會隨深度增加而提高以外,和LET呈現高度的線性關係。因此進行質子治療時除了考慮不同深度下劑量的變化,或許也可以將細胞的損傷及修復變化納入考量。

關鍵字

質子治療 SOBP 雙股螺旋斷裂 RBE

並列摘要


Proton therapy has the characteristic that is conformed the tumor region. After the proton ions enter the human body, the dose absorption will slowly increase with depth, and it will reach to a peak near the end of the track of the particle, which is called Bragg peak. Therefore, before reaching the treatment target, proton beams continue to give radiation dose to nearby healthy tissues. Through this study, we calculated the DNA damage and repair caused by 62 MeV protons at different depths. In addition, the changes of the relative biological effectiveness (RBE) values at different depths will be compared and the relationship between RBE and linear energy transfer (LET) will be discussed. In this study, Monte Carlo damage simulation, MCDS and Monte Carlo excision repair, MCER were used to perform computer simulations to observe the DNA damage and repair outcome caused by 62 MeV monoenergetic (pristine) and modulated (spread-out Bragg peak, SOBP) proton beams at different depths. According to the MCDS simulation results, as the depth increases, the yields of total DNA damage decrease by 0.7-17.09%, while the yields of double-strand breaks (DSB) induction increase by 3.44-80.8%. Compared with the results at the surface depth, the yields of DSB induction at the Bragg peak depth increase approximately 1.5-1.8 times. In addition, through MCER simulation, the results show that as the depth increases, the probability of correct repair decreases, and the probability of mutation and DSB conversion increase. The RBE values for the DSB conversion and induction increase as the depth increases, and both have a highly linear relationship with LET, and both R-square values are about 0.99. As the depth approaches to the Bragg peak, the yields of total damage will decrease, and the yields of DSB (including DSB induction and conversion) will increase accordingly. In addition, the RBE value increase as depth increases, and LET presents a highly linear relationship. Therefore, in addition to dosimetry at different depths, proton therapy may also take into account the effects of DNA damage and repair.

並列關鍵字

proton therapy SOBP DSB RBE

參考文獻


[1] Chaudhary, Pankaj, et al. "Relative biological effectiveness variation along monoenergetic and modulated Bragg peaks of a 62-MeV therapeutic proton beam: a preclinical assessment." International Journal of Radiation Oncology* Biology* Physics 90.1 (2014): 27-35.
[2] Lee, Catherine T., et al. "Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: how do protons compare with other conformal techniques?." International Journal of Radiation Oncology* Biology* Physics 63.2 (2005): 362-372.
[3] Mouw, Kent W., et al. "Proton radiation therapy for the treatment of retinoblastoma." International Journal of Radiation Oncology* Biology* Physics 90.4 (2014): 863-869.
[4] Mishra, Kavita K., and Inder K. Daftari. "Proton therapy for the management of uveal melanoma and other ocular tumors." Chin Clin Oncol 5.4 (2016): 50.
[5] Damato B, Kacperek A, Chopra M, et al. Proton beam radiotherapy of choroidal melanoma: the Liverpool-Clatterbridge experience. Int J Radiat Oncol Biol Phys 2005;62:1405-11.

延伸閱讀