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Zinc-induced resistance to alkylating agents: lack of correlation between cell survival and metallothionein content

Journal Article · · Toxicol. Appl. Pharmacol.; (United States)
Suspension cultures of line CHO Chinese hamster cells and three derived sublines which differ in their capacity to induce synthesis of metallothionein (MT) by at least a factor of 40-fold were exposed to 100 ..mu..m ZnCl/sub 2/ prior to treatment with the alkylating agent iodoacetate, and cytotoxicity was determined by measuring colony-forming ability. Three of the four types of cells exhibited an 8- to 10-fold enhancement in survival when pretreated with zinc, but there were two lines of evidence that suggested that the enhanced survival was not attributable to metallothionein. The only cell in the series which failed to exhibit increased survival when pretreated with zinc was the Cd/sup r/2ClO cell which is readily induced to synthesize MT when treated with ZnCl/sub 2/. An even stronger indication that metallothionein did not play a major role in the protective response was provided by the observation that CHO cells were protected by pretreatment with zinc, even though they are unable to induce synthesis of MT as a result of exposure to that metal. These results suggest the existence of a novel, zinc-inducible mechanism which protects cells against the toxic effects of alkylating agents.
Research Organization:
Los Alamos National Lab., NM
OSTI ID:
6241569
Journal Information:
Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 64; ISSN TXAPA
Country of Publication:
United States
Language:
English