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Asparagine Biosynthesis in Human KB Tumor Cells: Inhibitor Studies with Asparagine and Glutamine Antagonists

Solid Tumor Service, Medicine Branch, National Cancer Institute, Bethesda, Maryland 20014

Resistance to L-asparagine depletion in tumor cells has been correlated with asparagine biosynthesis mediated by the enzyme asparagine synthetase. In this study, we describe certain characteristics of the asparagine synthetase of the KB human tumor cell carried in tissue culture. The KB enzyme is similar to that of other mammalian tumors in terms of cofactor requirements and inhibition by L-asparagine antagonists. The in vitro effect of glutamine antagonists on enzyme activity was determined. 6-Diazo-5-oxo-L-norleucine and azotomycin were shown to be effective inhibitors, but azaserine was relatively ineffective. The implications of combining such drugs with the antineoplastic agent L-asparaginase are discussed.

Received 9/15/69. Accepted 11/ 5/69.