PAa细胞内O^6-甲基鸟嘌呤DNA甲基转移酶与放射敏感性的关系

Relationship between O^6-methylguanine-DNA Methyltransferase and Radiation sensitivity in PAa cells

目的:探讨PAa细胞内O6 甲基鸟嘌呤DNA甲基转移酶(O6 MT)与放射敏感性的关系。方法:建立裸 鼠人肺腺癌PAa模型,分为4组,从接种日始,Ⅰ、Ⅱ、Ⅲ、Ⅳ组裸鼠每天灌服0.2ml无菌生理盐水,35dⅡ、Ⅳ 组腹腔注射2mg链脲菌素(STZ),36d予Ⅲ、Ⅳ组瘤体10GyX线照射,测瘤体直径、O6 MT含量、MGMT染色 及细胞病理学镜检。结果:4组中O6 MT含量Ⅰ组最高,Ⅳ组最少,Ⅳ组与Ⅰ、Ⅱ组相比差异显著,Ⅳ组与Ⅲ组 相比差异也显著(P<0.05);MGMT染色强度变化与O6 MT含量一致。瘤体生长Ⅰ、Ⅱ组瘤体放疗后4d后明 显增大,Ⅲ组6d后明显增大,与Ⅰ、Ⅱ组相比增长减慢,Ⅳ组瘤体在4d后明显减少;病理学镜检Ⅲ组见小的散 在坏死灶,Ⅳ组坏死区域增加。通过对O6 MT活性、MGMT染色强度与病理学镜检、瘤体大小对比,细胞内O6 MT含量与放射敏感性密切相关,O6 MT含量低组别放疗效果好。结论:O6 MT含量决定其放射敏感性,据O6 MT活性高低预测其放射敏感性,STZ可提高放疗疗效。

Research Objectve:To study the relationship between O 6 methylguanine DNA methyltransferase (O 6 MT) and radiosensitivity in PAa cells.Methods:Nude mice of human lung adenocarcinoma (PAa) models were erected and divided into 4 groups.0.2 ml distilled germfree brine was perfused to mice of group Ⅰ、Ⅱ、Ⅳ and Ⅳ from the day inoculating,2 mg STZ was injected into celiac cawity in groupⅡ、Ⅳ on day 35,radiotherapy of 10 Gy X ray was performed to group Ⅲ、Ⅳ on day 36 .Measure tumor diameter、concentration of O 6 MT、MGMT coloration and observe cellular pathology under nicsoscope.Results:The concentration of O 6 MT in groupⅠwas the highest among the 3 groups;the concentration in group Ⅲ was the lowest,the difference between group Ⅳ and group Ⅲ was obvious;various intensities of MGMT coloration accorded with the concentration of O 6 MT.The growth of tumor:Accretion of tumor in group Ⅰ、Ⅱ were notable from the 4th day after radiotherapy,so was the group Ⅲ from the 6th day,but mnd slower compared with group Ⅰ、Ⅱ;the tumor of group Ⅳ reduced remarkably on 4th day.Pathologic observation reuealed:Small dispersed necrotic focuses coold be seen in group Ⅲ,necrotic region was larger in group Ⅳ.Comparison between O 6 MT activity、intensity of MGMT coloration and pathology 、size of tumor showed that concentration of O 6 MT had close relationship with radiosensitivity,therapeutic effect in group having low level of O 6 MT.Conclusions:The concentration of O 6 MT determins the,radiosensitivity which can be forcasted according to the level of O 6 MT and STZ improves the therapeutic effect of radiotherapy.