Gupta R S
McMaster University, Department of Biochemistry, Hamilton, Ontario, Canada.
Biochem Biophys Res Commun. 1988 Jun 16;153(2):598-605. doi: 10.1016/s0006-291x(88)81137-9.
In comparison to human cells, cell lines of Chinese hamster and mouse origin exhibit between 10-50-fold resistance to a number of different drugs (viz. actinomycin D, daunomycin, chromomycin A3, colchicine, maytansine, mithramycin, puromycin, rhodamine 123, vinblastine and taxol). Studies with a representative Chinese hamster line (CHO) and a single-step multidrug resistant (MDR) mutant of human (HeLa) cells show that: (i) In comparison to the sensitive human cells, both cell lines show a comparable degree of resistance to the above mentioned drugs; (ii) In the presence of non-toxic dosage of verapamil, the drug-resistance phenotype of both cell lines is completely reversed; (iii) Both these cell lines showed greatly reduced uptake/intracellular levels of 3H-daunomycin, 3H-puromycin and 3H-vinblastine, which was restored to sensitive human cell's level in the presence of non-toxic doses of verapamil. The striking similarity in the behaviour of the naturally resistant Chinese hamster cells and a human MDR cell line with regard to the above characteristics, strongly suggests that the species-related differences in sensitivity to the above drugs result from a similar mechanism as that responsible for the MDR phenotype.
与人类细胞相比,源自中国仓鼠和小鼠的细胞系对多种不同药物(即放线菌素D、柔红霉素、色霉素A3、秋水仙碱、美登素、光神霉素、嘌呤霉素、罗丹明123、长春碱和紫杉醇)表现出10至50倍的耐药性。对一个具有代表性的中国仓鼠细胞系(CHO)和人类(HeLa)细胞的单步多药耐药(MDR)突变体进行的研究表明:(i)与敏感的人类细胞相比,这两种细胞系对上述药物表现出相当程度的耐药性;(ii)在无毒剂量的维拉帕米存在下,这两种细胞系的耐药表型完全逆转;(iii)这两种细胞系对3H-柔红霉素、3H-嘌呤霉素和3H-长春碱的摄取/细胞内水平大大降低,在无毒剂量的维拉帕米存在下恢复到敏感人类细胞的水平。天然耐药的中国仓鼠细胞和人类MDR细胞系在上述特征方面行为的惊人相似性,强烈表明物种对上述药物敏感性的差异源于与MDR表型相同的机制。