Klein P, Pool-Zobel B L, Yalkinoglu O, Schlehofer J R
German Cancer Research Center, Institute of Chemotherapy and Toxicology, Heidelberg.
Mutat Res. 1990 Oct;232(2):183-90. doi: 10.1016/0027-5107(90)90123-l.
DNA amplification is a frequently observed event in continuous cell lines and in tumors. It is likely that a common mechanism underlies the amplification of specific DNA sequences which confer drug resistance and genes which give a growth advantage to the tumor. To find a correlation between the induction of DNA amplification by chemicals and morphological cell transformation we treated Syrian hamster embryo (SHE) cells with diverse antineoplastic agents of different classes. Analysis of these agents seems to be important since they are potentially carcinogenic and resistance inducing. For the measurement of DNA amplification we established a new system using adeno-associated virus type 2 (AAV)-infected primary SHE cells as target cells and amplification of viral DNA as marker of DNA amplification. Simultaneously we determined morphological cell transformation in SHE cells. Our findings demonstrate that there is only a limited correlation between the induction of AAV DNA amplification and the morphological cell transformation in SHE cells. The newly established system of AAV DNA amplification appears to be a useful tool for the investigation of drug resistance in target cells of choice.
DNA扩增是连续细胞系和肿瘤中经常观察到的现象。特定DNA序列(赋予耐药性)和基因(赋予肿瘤生长优势)的扩增可能存在共同机制。为了找出化学物质诱导DNA扩增与细胞形态转化之间的相关性,我们用不同类别的多种抗肿瘤药物处理叙利亚仓鼠胚胎(SHE)细胞。对这些药物进行分析似乎很重要,因为它们具有潜在致癌性和诱导耐药性。为了测量DNA扩增,我们建立了一个新系统,使用腺相关病毒2型(AAV)感染的原代SHE细胞作为靶细胞,并将病毒DNA扩增作为DNA扩增的标志物。同时,我们测定了SHE细胞中的细胞形态转化。我们的研究结果表明,AAV DNA扩增的诱导与SHE细胞中的细胞形态转化之间只有有限的相关性。新建立的AAV DNA扩增系统似乎是研究所选靶细胞中耐药性的有用工具。