Stammler G, Pommerenke E W, Mattern J, Volm M
German Cancer Research Center, Heidelberg.
Carcinogenesis. 1995 Sep;16(9):2051-5. doi: 10.1093/carcin/16.9.2051.
In this report the effects of single doses of ionizing radiation on the mRNA expression of several proteins involved in multiple drug resistance were analyzed. Murine NIH 3T3 cells treated with single doses of 5, 10 and 20 Gy during the time interval from 1.5 to 72 h after irradiation were compared with their corresponding controls at the same points of time. The glutathione S-transferase-pi (GST pi) level was elevated in cells treated with 10 or 20 Gy from 24 to 72 h after irradiation compared with the control. Topoisomerase II alpha and thymidylate synthase were decreased in irradiated cells 24-72 h after exposure. These down-regulations were associated with cellular proliferation, determined by mRNA expression of the proliferation marker histone 3. Irradiated cells exhibited no alteration in the P-glycoprotein or glutathione peroxidase mRNA content. The finding that GST pi mRNA was overexpressed after irradiation was validated by investigations on a human lung carcinoma cell line (LXF 289) on the mRNA and protein level. Thus, our results indicate that irradiation alters the expression of proteins involved in multidrug resistance and may, therefore, play a role in clinical drug response.
在本报告中，分析了单次剂量电离辐射对几种参与多药耐药性的蛋白质的mRNA表达的影响。将在照射后1.5至72小时的时间间隔内接受5、10和20 Gy单次剂量处理的小鼠NIH 3T3细胞与其在相同时间点的相应对照进行比较。与对照相比，在照射后24至72小时，用10或20 Gy处理的细胞中谷胱甘肽S-转移酶-pi（GST pi）水平升高。照射后24 - 72小时，照射细胞中的拓扑异构酶IIα和胸苷酸合成酶减少。这些下调与细胞增殖相关，细胞增殖由增殖标志物组蛋白3的mRNA表达确定。照射细胞的P-糖蛋白或谷胱甘肽过氧化物酶mRNA含量没有变化。通过对人肺癌细胞系（LXF 289）的mRNA和蛋白质水平研究，证实了照射后GST pi mRNA过度表达这一发现。因此，我们的结果表明，辐射会改变参与多药耐药性的蛋白质的表达，因此可能在临床药物反应中发挥作用。
