Zinc-induced resistance to alkylating agent toxicity.

Suspension cultures of Chinese hamster ovary cells and three derived cadmium-resistant variants were exposed to 100 microM ZnCl2 prior to treatment with the alkylating agent, melphalan, and cytotoxicity was then determined by measuring colony-forming ability. A 10-fold or greater enhancement in survival of all zinc-pretreated cultures subsequently exposed to melphalan was observed which was unrelated to metallothionein induction capacity. Although the maximum achievable protection afforded by zinc occurred in cultures receiving 100 microM ZnCl2, concentrations of zinc only slightly in excess of levels found in human serum were shown to provide a 4.5-fold enhancement of protection, indicating that the phenomenon can also be induced at physiologically reasonable levels. These results suggest the existence of a novel zinc-inducible mechanism which protects cells against the toxic effects of alkylating agents.