GENETIC ANALYSIS OF THE MULTIPLE DRUG RESISTANCE PHENOTYPE IN TUMOR CELLS

在人类癌症的化疗过程中，变异是 对多种药物的耐药性频繁出现。我们一直在调查 人类多效性耐药的遗传和生化基础 肿瘤细胞对化疗药物的影响。一种使用培养物的模型系统 KB细胞是一种人类癌细胞系，在该细胞系中突变株 独立选择的细胞，以抵抗高水平的 秋水仙素、阿霉素或长春花碱也被发现是 对秋水仙碱、阿霉素、长春新碱、长春花碱、 嘌呤霉素和放线菌素-D这些药物的遗传连锁 秋水仙素选育品系的抗性已经通过它们的 并列出现、并列反转、共显性和协区分性 在体细胞杂交中，以及通过DNA介导的基因转移进行共转移。 积聚的几种药物涉及的多重 在KB细胞中，耐药表型已经被证明是减少的。 耐药性与一组糖蛋白家族的缺失有关 用多克隆和多克隆技术检测细胞表面分子量为70-8万 单抗，在某些情况下，出现低分子 重量蛋白(P21)。耐药性也与扩增有关。 通过凝胶内复性技术或在 Southern杂交技术在耐药基因扩增DNA克隆中的应用 仓鼠细胞。

During the course of chemotherapy of human cancers, variants which are resistant to multiple drugs frequently arise. We have been investigation the genetic and biochemcial basis for this pleiotropic resistance of human tumor cells to chemotherapeutic agents. A model system using the cultured KB cell, a human carcinoma cell line, has been developed in which mutant cells selected independently for resistance to high levels of either colchicine, adriamycin or vinblastine have also been found to be cross-resistant to colchicine, adriamycin, vincristine, vinblastine, puromycin and actinomycin-D. Genetic linkage of these multiple drug resistances in the colchicine-selected line has been demonstrated by their coordiante appearance, coordinate reversion, codominance and cosegregation in somatic cell hybrids, and cotransfer by DNA-mediated gene transfer. Accumulation of several of the drugs involved in the multiple drug-resistance phenotype has been shown to be reduced in the KB cells. Drug-resistance correlates with the loss of a family of glycoproteins of molecular weights 70-80,000 on the cell surface detected by polyclonal and monoclonal antibodies and, in some cases, the appearance of a low molecular weight protein (p21). Drug-resistance also correlates with amplification of DNA segment detected either by an in gel renaturation technique or on Southern blots using probes cloned from amplified DNA in drug-resistant hamster cells.