Technetium-99m產生之間接作用所造成的損傷及修復之研究

除了游離輻射導致的DNA雙股螺旋斷裂損傷，非雙股螺旋斷裂損傷可能在經由鹼基切除修復和核苷酸切除修復的過程中，修復錯誤導致突變，也可能修復失敗而導致額外的雙股螺旋斷裂產生。這項研究的目的為利用蒙地卡羅模擬方法，研究 Technetium-99m 激發的電子，在細胞中造成的雙股螺旋斷裂損傷 (prompt DSBs)和其他因錯誤修復進而產生的雙股螺旋斷裂損傷(enzymatic DSBs)的產量，並研究不同濃度的二甲基亞碸(Dimethyl sulfoxide, DMSO)對細胞的輻射保護效果及損傷修復效果。 利用蒙地卡羅損傷模擬程式(Monte Carlo Damage Simulation, MCDS)及蒙地卡羅切除修復程式 (Monte Carlo Excision Repair, MCER)來進行模擬，本研究將核種對細胞 DNA 的各種損傷路徑模擬出來，並得到其Total SSB (Single strand break)以及Total DSB (Double strand break)的量值(per Gy per Gbp)，也模擬出其他不同種類的 DNA 損傷百分比，以及模擬出Technetium-99m在各個能量的LET(Linear energy transfer)值；在損傷修復的模擬，模擬出損傷經過鹼切除修復(Base excision repair, BER)和核苷酸切除修復(Nucleotide excision repair, NER)的結果，可以分別模擬出四種不同的修復途徑，分別為SP (short patch)/BER、LP (long patch)/BER、NER/SP BER及NER/LP BER，並計算出每種修復途徑的 DNA 修復正確修復機率(correct repair)、產生突變機率(mutation)及修復失敗產生額外的雙股螺旋斷裂機率(formation of an enzymatic DSBs)。 在損傷量的模擬結果，加入 0.2M 的 DMSO 後，total SSB 損傷量降至原始損傷量的39%，total DSB損傷量降至原始損傷量的5%，總損傷降至原始總損傷的57%，在LET值的模擬結果，Technetium-99m的LET值為14.38 keV/ μm。在細胞修復的模擬結果，加入0.2M的DMSO可以讓非雙股螺旋斷裂的損傷成功修復率提升11-61%，產生突變機率下降79%-90%，修復失敗導致額外的雙股螺旋斷裂損傷機率下降86-89%。因錯誤修復進而產生的雙股螺旋斷裂損傷(enzymatic DSBs)為14.35 per Gy per Gbp，加入 0.2 M DMSO 後損傷量降至 0.95 per Gy per Gbp，下降了93%。

In addition to DSBs induced by ionizing radiation, misrepair of non-DSB clustered damage can contribute extra DSBs, which converted from DNA misrepair via pathways for base excision repair and nucleotide excision repair, leading to mutagenesis or cell death. This study aimed to use the Monte Carlo simulation method to quantify the production of double-strand breaks (prompt DSBs) and extra DSBs converted from DNA misrepair (enzymatic DSBs), induced by electrons of Technetium-99m. The effects of different concentrations of dimethyl sulfoxide (DMSO) on cell protection and damage repair were also studied.We used Monte Carlo Damage Simulation (MCDS) and Monte Carlo Excision Repair (MCER) to perform the simulation. MCDS can simulate the yields of clustered damage in a cell, including BD (base damage), SSB (single strand break), and DSB (double strand break). MCDS also provided estimates of damage in the presence of DMSO, and simulated the LET of Technetium-99m of each energy. MCER was used to provide the probability of the repair outcomes in the BER (base excision repair) and NER (nucleotide excision repair) pathways for DNA damage, and can simulate four different repair pathways, respectively, including SP (short patch)/BER, LP(long patch)/BER, NER/SP BER and NER/LP BER, and calculate the correct repair rate (COR), mutation rate (MUT) and repair failure leading formation of an enzymatic DSBs (DSB) rate of each repair pathway.In the simulation results of MCDS, after adding 0.2M of DMSO, the total SSB damage was reduced to 39% of the original damage, the total DSB damage was reduced to 5% of the original damage, and the total damage was reduced to 57% of the original total damage. In the MCER simulation results, the addition of 0.2M DMSO can increase the successful repair rate of non-DSBs damage by 11-61%, and reduce the probability of mutations by 79-90%, and the repair failure rate drops by 86-89%. The enzymatic DSBs was 14.35 per Gy per Gbp. After adding 0.2 M DMSO, the damage decreased to 0.95 per Gy per Gbp, decreasing 93% of the originals.