Original Articles The Influence of Desmethylmisonidazole and Adriamycin on the Potentially Lethal Damage of Post Irradiated ME180 Cells

Desmethylmisonidazole及Adriamycin對於放射線照射後之ME180細胞發生潛在性致死損傷之影響

黃經民(Jing-Min Hwang) ； 許文林(Wen-Lin Hsu) ； 楊光明(Kuang-Ming Yang) ； 陳家福(Chia-Fu Chen) ； 鄭美滿(Mei-Man Cheng) ； 任益民(Yee-Min Jen) ； 趙壯飛(Chung-Faye Chao) ； 陳光耀(Kuang-Yao Chen)

《Journal of Medical Sciences》 14卷4期 (1994/02) Pp. 217-236

摘要

不同培養期之ME180子宮頸癌細胞輻射線敏感度（Do值）已被測知。結果顯示經過1~12小時培養之細胞其Do值介於2.29~3.05 Gy之間，並無顯著差異，至於培養24小時之細胞對輻射線較不敏感。為了解發生潛在性致死損傷（PLD）之程度，ME180細胞接受放射線照射後分為三組，分別是：（1）以PBS溶液處理，（2）立即移植到另一新鮮培養液內，（3）或停留在原照射培養液內4小時。其中立即移植組之Do值為1.90 Gy，而PBS組之Do值為1.50 Gy，顯示了PLD的確發生。至於置留原培養液組之Do值為2.08 Gy，顯示了PLD之修復。此外，平原生長期之ME180細胞較指數生長期細胞表現了較少之PLD及較多的PLD修復。本實驗所求得之ME180細胞氧促進比值（OER值）約為2.17。缺氧環境能降低照射後細胞發生PLD，並增加細胞對於PLD之修復。與缺氧實驗各對照組相比，經Adriamycin（1μg/ml）處理之ME180細胞，照射後產生之生存曲線Do值為2.63 Gy，以PBS溶液處理後則Do值降為2.30 Gy，顯示PLD之表現增強，然而置留在原培養液之細胞其Do值為3.29，顯示PLD修復現象被抑制。若將DMM（1000Μm；Desmethylmisonidazole，一種放射敏感藥物）單獨加入培養液內，亦產生與Adriamycin類似的結果。同時將Adriamycin及DMM合併給予ME180細胞，則各組照射後細胞的生存分數都會下降，且此處理模式對於照射後細胞發生PLD（Do值由2.51 Gy降到1.96Gy）及PLD修復（Do值由2.51 Gy升到2.91 Gy）分別有更強的增強與抑制能力。因此，DMM及Adriamycin不論單獨或合併使用，都能加強照射後子宮頸癌細胞PLD之表現，對於未來臨床之放射治療將會有一正面的效應。

關鍵字

ME180細胞 ； 細胞齡 ； 潛在性致死損傷 ； 潛在性致死損傷修復

並列摘要

ME180 cervical carcinoma cells of different culture ages were collected to evaluate their radiosensitivity. The results showed that there is no significant radiosensitivity difference among cells of 1 hr to 12 hrs of age with Do values (the radiation dose required to reduce cell survival from 0.1 to 0.037) ranging from 2.29 to 3.05 Gy. However, cells collected from 24 hrs of culture are least sensitive to x-irradiation. ME180 cells were irradiated at room temperature under aerobic conditions to evaluate their PLD (potentially lethal damage). After irradiation, the were treated with hypertonic PBS (phosphate buffer solution), plated immediately, or still incubated for 4 hours in original medium. The immediately pated group showed a Do value of 1.90 Gy, however, the PBS group showed a Do value of 1.50 Gy, suggesting the occurrence of PLD, and the still incubated group had a Do value of 2.08 Gy, displaying a phenomenon of PLD repair. In addition the results also revealed that ME180 cells of plateau phase displayed more PLD repair and less PLD than those cells of log phase. ME180 cells were irradiated under hypoxic and oxygenated conditions and an OER (oxygen enhancement ratio) value of roughly 2.17 was calculated. The effects of hypoxic condition on PLD repair of ME180 cells were also studied. Hypoxia induced less PLD and more PLD repair. Apart from that, the effects of adriamycin (1 ug/ml) on PLD repair of ME180 cells were also evaluated. The immediately plated group showed a Do value of 2.63 Gy; however, the PBS group showed a Do value of 2.30 Gy, suggesting an enhancement of PLD, and the still incubated group had a Do value of 3.29 Gy, displaying a decrease of PLD repair. The effect of DMM (1000 uM, one of the 2-nitroimidazole radiosensitizer group) on PLD repair of ME180 cells was studied. Like adriamycin, DMM also lowered the survivals, enhanced PLD, and decreased PLD repair. In addition, the combined effects of DMM (1000 nM) and adriamycin (1 ug/ml)on PLD repair of ME180 cells after exposure to radiation were further evaluated. Similar to adriamycin and DMM respectively, combined treatment also lowered the survivals of each theatment groups. However, the combined group showed more significant inhibitory effects of PLD repair. The immediately plated group showed a Do value of 2.51 Gy; nevertheless, the PBS group showed a Do value of 1.96 Gy, suggesting a further enhancement of PLD, and the still incubated group had a Do value of 2.91 Gy, displaying a further decrease of PLD repair. Therefore, PLD of irradiated hypoxic ME180 cells was enhanced by either combining or separately using adriamycin or DMM. This could possibly have positive effects on clinical radiotherapy.

並列關鍵字

ME180 cells ； cell age ； potentially lethal damage (PLD) ； repair of potentially lethal damage (PLD repair) ； desmethylmisonidazole (DMM) ； adriamycin