62 MeV質子在不同DMSO與氧氣濃度下照射細胞所造成的損傷與修復研究

質子因為具有特殊的劑量累積特性，所以在近幾年來被應用在放射治療中，質子在進入人體時，在射程的入口處具有較低的吸收劑量，而到了射程末端時，吸收劑量會急遽上升，之後快速下降，此深度劑量曲線稱為「布拉格曲線」，透過此特性，在腫瘤區域累積高輻射劑量的同時，周圍正常組織的劑量可大幅降低。然而腫瘤組織的含氧量卻會影響到放射治療的效果，此外，雖然在質子治療中，腫瘤周圍正常組織的劑量相對於光子治療來說少了很多，但是仍會受到輻射影響，因此本研究目的為觀察在不同氧氣濃度與使用輻射保護劑時，62 MeV質子照射細胞所產生的DNA損傷變化。 在本研究中使用蒙地卡羅損傷模擬(MCDS)與蒙地卡羅切除修復模擬(MCER)來模擬62 MeV質子在不同的氧氣濃度與不同的DMSO濃度下，照射細胞後所產生的DNA損傷與修復後的結果變化。 在MCDS的結果中發現，隨著氧氣濃度的降低，所有類型的DNA損傷都下降，當氧氣濃度從21%下降至0.01%時，雙股斷裂(DSB)減少了92%，除此之外，在加入DMSO時也會減少DNA損傷量。在MCER模擬中則是觀察到加入DMSO可以增加正確修復的機率，降低突變與DSB轉換的機率，而且使用DMSO也可以有效減少DSB轉換量。DMSO的濃度變化也會對RBE有所影響，當DMSO濃度從0 M增加到0.2 M時，RBE會持續下降。 當腫瘤為極度缺氧的狀態時，會降低放射治療的效果，而在自由基清除劑的部分，當使用DMSO時，可以減少DNA損傷量，因此在放射治療時，對腫瘤組織使用輻射增敏劑，而對周圍正常的組織使用DMSO的話，可以增進治療效果，減少對正常組織的傷害。

Protons have been used in the radiation therapy in recent years because of their special accumulated dose. When protons enter the body, they have a lower absorbed dose at the entrance of the range, and when they reach the end of the range, the absorbed dose will be higher. The absorbed dose rises sharply and then drops rapidly. This depth dose curve is called "Bragg curve", so the dose accumulated in the tumor can be increased, while the dose accumulated in the normal tissue can be reduced. Nevertheless, the oxygen concentration of the tumor can affect the effect of radiation therapy. Additionally, in the proton therapy, although the dose accumulated in the normal tissue is lower than that of photon therapy, the normal tissue will still be damaged. Therefore, the purpose of this study is to observe the changes in DNA damage caused by 62 MeV protons at different oxygen and DMSO concentrations. In this study, Monte Carlo damage simulation (MCDS) and Monte Carlo excision repair (MCER) are used to simulate the DNA damage caused by 62 MeV protons at different oxygen concentrations and different DMSO concentrations. In the MCDS, all types of DNA damage are decreased when the oxygen concentration decreases, and double-strand breaks (DSBs) decrease by 92% when the oxygen concentration decreases from 21% to 0.01%. The amount of DNA damage is also decreased when DMSO is added. In the MCER, it is observed that adding DMSO can increase the probability of correct repair and reduce the probability of mutation and DSB conversion. Additionally, the use of DMSO can also reduce the amount of DSB conversion. DMSO also has an effect on RBE, the RBE can be decreased when the DMSO concentration increases from 0 M to 0.2 M. When the tumor is extremely hypoxic, the effect of radiation therapy is reduced, and when DMSO is used, the amount of DNA damage can be reduced, so in radiation therapy, the use of radiation sensitizer on tumor tissue and the use of DMSO on surrounding normal tissue can improve the therapeutic effect and reduce damage to normal tissue.