Isolation of a Gene Associated with Resistance to Cisplatin
Cisplatin (DDP) is one of the most widely used antineoplastic agents for the treatment of human cancer. It is effective against a broad spectrum of malignancies including testicular, ovarian, head and neck, bladder, and some forms of lung cancer. This usefulness is frequently obviated by the development of resistance in treated tumors (1). DDP resistance is expressed co-dominantly and is phenotypically stable for long periods in the absence of selection, implying a genetic basis (2). Both in vivo and in vitro selection with DDP usually result in levels of resistance on the order of 2 to 4-fold; clinically relevant but markedly less than that encountered with many antimetabolites and drugs associated with the multiple drug resistance phenotype mediated by the mdr 1 gene (3,4). The molecular basis of this resistance is not understood, though factors identified as capable of contributing to it include diminished DDP uptake, elevated glutathione or metallothioneins, and enhanced repair of DDP-DNA adducts (2).
KeywordsHuman Ovarian Carcinoma Cell Human Ovarian Carcinoma Cell Line DG44 Cell Chinese Hamster Ovary DG44 Cell Multiple Drug Resistance Phenotype
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