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The Effect of Dietary Mineral Supplements of the Rat on the Antitumor Activity of 3-Ethoxy-2-oxobutyraldehyde Bis(thiosemicarbazone)¹

Biochemical Research Division, The Upjohn Company, Kalamazoo, Michigan

The antitumor activity and toxicity of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone) (KTS) in rats bearing Walker 256 nitrogen-mustard-resistant carcinosarcoma (W-256-NMR) has been shown to be directly dependent on the dietary intake of cupric ion. The critical effect of environmental and dietary trace metals on KTS activity is further indicated by the fact that zinc and cobaltous ions may influence both toxicity and antitumor action of the drug when copper is present.

Copper is critical for KTS activity whether the drug is given orally or intraperitoneally. Copper was shown to be without effect on W-256-NMR in the absence of drug, while zinc was shown to be necessary for W-256-NMR growth as well as rat growth.

¹ A preliminary report has been presented (3).

² Present address: Kettering Laboratory, College of Medicine, University of Cincinnati, Cincinnati, Ohio 45219. This address should be used in all correspondence.

Received 8/24/66. Accepted 2/16/67.