With Reference to Blastogenesis Inhibition by L-Asparaginase

The interpretation that L-asparaginase is a selective inhibitor directed only against neoplastic tissues, particularly lymphoid neoplastic tissue, does not seem to be entirely true. In fact: 1.1. Schreck [1] showed that not only leukemic but also normal lymphocytes in culture are damaged if L-asparaginase is added to the medium. 1.2. Broome [2] observed that the content of free asparagine quickly diminishes in the thymus and in the spleen of the C3H mice treated with L-asparaginase. 1.3. It appeared that some rapidly growing tissues are impaired by L-asparaginase. This effect was observed in rabbit embryos and fetuses (Adamson and Fabro [3]), and in the liver of partially hepatectomized rats (Becker and Broome [4], Grundmann [5]), as well as in the proliferation kinetics of human bone marrow in culture (Boll and Reckers [6]). Also the growth of HeLa cells in culture became highly inhibited by EC-2 asparaginase (Oerkermann and Hirschmann [7]). 1.4. Astaldi, Burgio et al. [8] showed that E. coli L-asparaginase intensely inhibits blastic transformation of human peripheral blood lymphocytes in the PHA-culture system. 1.5. McElwain and Hayward [9] were then able to show the same effect also when the enzyme is administered i. v., and the lymphocytes are subsequently removed and cultivated in the PHA-medium.