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 surv...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1982-08, Vol.42 (8), p.2980
Main Authors: Tobey, R A, Enger, M D, Griffith, J K, Hildebrand, C E
Format: Article
Language:English
Subjects:
Animals
Cadmium - pharmacology
Cell Division - drug effects
Cell Line
Cell Survival - drug effects
Chlorides
Cricetinae
Cricetulus
Drug Resistance
Female
Kinetics
Melphalan - pharmacology
Ovary
Zinc - pharmacology
Zinc Compounds
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Summary: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.
ISSN:0008-5472