ABSTRACT
The asparagine synthetase (AS) system has many advantages for somatic cell genetic studies, since the same parental background can be used to select mutants that have various levels of AS activity, ranging from complete absence to 300-fold overproduction of AS. To isolate mutants of Chinese hamster ovary and human cell lines that have alterations in the expression of AS activity, amino acid analogues of the substrates of AS were used. Mutants resistant to either β-aspartyl hydroxamate, an aspartic acid analogue, or albizziin, a glutamine analogue, exhibit elevated levels of AS activity. Certain tumor cells are asparagine auxotrophs, since they exhibit little or no AS activity and rely on the surrounding medium as a source of exogenous asparagine. The mechanism responsible for the lack of activity of AS in the sensitive leukemic cells and overproduction in the asparaginase-resistant variants is of clinical importance for the treatment of acute lymphoblastic leukemia patients both initially and during relapse.
