Nutritional requirements of human leukemic cells: Asparagine requirements and the effect of l-asparaginase

Abstract

Eight cultures of human lymphoblastic cells have been examined with respect to l-asparagine requirements. Although none of these cultures required exogenous l-asparagine for log-phase growth, or exhibited a metabolic response to exogenous l-asparagine, all were inhibited by l-asparaginase, both in the presence and absence of exogenous l-asparagine. Study of samples of l-asparaginase of known degrees of purity indicated that inhibition was related to specific enzyme activity, rather than to the possible presence of a non-specific “toxic factor”. The most likely explanation of these observations is that these human lymphoblastic cells have sufficient asparagine synthetase activity (which may be population-dependent) to satisfy their metabolic requirements for l-asparagine, and that l-asparaginase interferes with the utilization of this endogenous l-asparagine. It is suggested that the degree of asparagine synthetase activity exhibited by a given population of cells might be a better index of sensitivity to l-asparaginase than is the metabolic response of that population to exogenous l-asparagine.