Hrubisko M, McGown A T, Fox B W
CRC Dept of Experimental Chemotherapy, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, U.K.
Biochem Pharmacol. 1993 Jan 7;45(1):253-6. doi: 10.1016/0006-2952(93)90399-h.
The glutathione contents, glutathione S-transferase activities and metallothionein contents have been measured in a series of L1210 cell lines which show decreased sensitivities to platinum drugs. Resistance to cisplatinum cisDDP, cis-diamminedichloroplatinum (II)] and chip [ioproplatin, cisdichloro-bis-isopropylamine-trans dihydroxy platinum IV] was found to correlate with glutathione levels but not metallothionein. Conversely, resistance to tetraplatin was found to be correlated with metallothionein but not glutathione levels. However, depletion of glutathione by buthionine 1-sulphoximine sensitizes all cell lines to the effects of cisDDP, chip and tetraplatin [d,1-trans-tetrachloro-1,2-diamino-cyclohexanplatinum (IV)]. Inhibition of DNA repair by aphidicholin or caffeine also partially restored sensitivity to these platinum drugs. These results indicate the complexity of the changes occurring upon the development of drug resistance.
在一系列对铂类药物敏感性降低的L1210细胞系中，已测定了谷胱甘肽含量、谷胱甘肽S-转移酶活性和金属硫蛋白含量。发现对顺铂（顺二氯二氨铂（II））和芯片（异丙铂，顺二氯双异丙胺反式二羟基铂（IV））的耐药性与谷胱甘肽水平相关，而与金属硫蛋白无关。相反，发现对四铂的耐药性与金属硫蛋白相关，而与谷胱甘肽水平无关。然而，丁硫氨酸亚砜胺使谷胱甘肽耗竭会使所有细胞系对顺铂、芯片和四铂（d，1-反式-四氯-1,2-二氨基环己烷铂（IV））的作用敏感。阿非胆碱或咖啡因对DNA修复的抑制也部分恢复了对这些铂类药物的敏感性。这些结果表明了耐药性产生时所发生变化的复杂性。
