METALLOTHIONEINS AND CELL-DEATH BY ANTICANCER DRUGS

Both pharmacologic and genetic methods are now available to manipulate intracellular levels of the protein thiol metallothionein. These appr oaches have begun to reveal the protective roles metallothioneins (MTs ) have against oxygen, nitrogen, and carbon-centered free radicals, as well as the contributory role of MT to resistance to a broad range of electrophilic therapeutic agents, including antineoplastic drugs. We suggest MTs are enlisted to act as primative antioxidant defense mecha nisms in mammalian cells and, thus, may have widespread importance in the biology of cell death.