Metallothioneins and Cisplatin Resistance
Intrinsic and acquired resistance to antineoplastic agents has severely limited our ability to cure solid tumors. Cis-diamminedichloroplatinum (cisplatin) represents one of the most efficacious agents for the treatment of solid tumors especially testicular, ovarian, bladder, and head and neck carcinomas. Once this neutral compound enters cells, the chloride ligands are exchanged for water or hydroxyl moieties and a biologically reactive bifunctional electrophile is produced. Like most of our effective antineoplastic agents, this aquated platinum compound can react with intracellular nucleophiles. Although only approximately 1% of the intracellular drug covalently reacts with DNA, there is extensive evidence implicating genomic DNA as the critical target for its cytotoxicity (Roberts and Thomson, 1979).
KeywordsChinese Hamster Ovary Cell Chinese Hamster Ovary Cell Transfectants Transient Resistance Drug Resistance Protein Pyridoxal Kinase
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