ROLE OF ASPARAGINE SYNTHETASE AND ASPARAGYL-TRANSFER RNA-SYNTHETASE IN THE CELL-KILLING ACTIVITY OF ASPARAGINASE IN CHINESE-HAMSTER OVARY CELL MUTANTS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (8) , 3104-3106
Abstract
The cell-killing activity of asparaginase [an antitumor enzyme produced from Escherichia coli] on 3 classes of Chinese hamster ovary cell mutants was examined: a mutant which overproduces asparagine synthetase (AH5); mutants defective in asparagine synthetase (N3 and N4); and mutants conditionally defective in asparagyl-tRNA synthetase (Asn 3, Asn 7 and Asn 9). The overproducer was more resistant to the cell-killing activity of asparaginase than wild-type Chinese hamster ovary cells, while mutants defective in asparagine synthetase were more sensitive. Surprisingly, the asparagyl-tRNA synthetase mutants were even more sensitive to asparaginase than the asparagine synthetase mutants. In a preliminary survey of 4 human lymphoid cell lines (RPMI 8402, RPMI 8392, B46M and Molt-4F) which showed dramatically different asparaginase sensitivity, sensitivity to the cell-killing activity of asparaginase was correlated with reduced levels of asparagine synthetase and not with reduced levels of asparagyl-tRNA synthetase.