Volm M, Zerban H, Mattern J, Efferth T
Department of Experimental Pathology, German Cancer Research Center, Heidelberg, FRG.
Carcinogenesis. 1990 Jan;11(1):169-72. doi: 10.1093/carcin/11.1.169.
The most frequently reported alteration of multidrug resistance (MDR) is the overexpression of the 170 kd membrane glycoprotein. An increased expression of the MDR-gene in pre-neoplastic and neoplastic liver lesions produced experimentally by different carcinogens has been reported. As shown in rat liver by stop experiments, specific carcinogen-induced alterations can be separated from non-specific, toxic changes. Therefore, we induced rat hepatocellular carcinomas with N-nitrosomorpholine and investigated whether expression of the MDR-gene also takes place in hepatocellular carcinomas after withdrawal of the carcinogen. Using mAb C219 against P-glycoprotein, both normal liver and hepatocellular carcinomas show specific immunoreactivity by means of immunofluorescence and immunohistochemistry. In hepatocellular carcinomas, however, the reaction is increased if compared to normal liver of untreated control animals. These results were confirmed by immunoblotting. Using the cDNA probe 1.5, a significant increase in MDR-gene transcripts was found in hepatocellular carcinomas as compared to normal liver.
多药耐药（MDR）最常报道的改变是170kd膜糖蛋白的过度表达。已有报道称，在由不同致癌物实验诱导产生的癌前和肿瘤性肝脏病变中，MDR基因的表达增加。如在大鼠肝脏中通过停药实验所示，特定致癌物诱导的改变可与非特异性毒性变化区分开来。因此，我们用N-亚硝基吗啉诱导大鼠肝细胞癌，并研究在撤去致癌物后，MDR基因是否也在肝细胞癌中表达。使用抗P-糖蛋白的单克隆抗体C219，通过免疫荧光和免疫组织化学方法，正常肝脏和肝细胞癌均显示出特异性免疫反应。然而，与未处理对照动物的正常肝脏相比，肝细胞癌中的反应增强。这些结果通过免疫印迹得到证实。使用cDNA探针1.5，发现与正常肝脏相比，肝细胞癌中MDR基因转录本显著增加。
