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The Effect of B Vitamin and Protein Intake of the Rat on the Antitumor Activity of 3-Ethoxy-2-oxobutyraldehyde Bis(thiosemicarbazone)¹

Biochemical Research Division, The Upjohn Company, Kalamazoo, Michigan

The relationship of water-soluble vitamin content of the diet, level of protein, and type of carbohydrate on the antitumor activity and toxicity of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone) (KTS) in rats was studied. The data illustrate the influence of these dietary constituents on the therapeutic action of KTS. Deficiency levels of thiamine and pantothenic acid were found in liver tissue of normal adult rats given high levels of KTS. Supplementation with excess thiamine and pantothenic acid in tumor-bearing rats reduced the growth restriction and enhanced the antitumor activity of the drug. Increasing the protein content of a basal, semipurified diet from 18% to 30% greatly diminished the possibility of cataract formation without affecting the antitumor action of KTS. The type of carbohydrate used in the diet seemed to be of little consequence, although glucose reduced somewhat the toxic effect of KTS on growth restriction.

¹ A preliminary report has been presented (10).

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.