Inhibition of ³H-Thymidine Incorporation into Rat Liver Nuclei by E. coli L-Asparaginase

Abstract

THERE have been numerous reports dealing with the anti-tumour activity of Escherichia coli L-asparaginase in the therapy of human leukaemia. It has been postulated that the agent is without toxic action on normal tissues and that it is specific for asparagine dependent tumour cells, but neither of these assumptions has been proved^1,2. When L-asparaginase was used in the treatment of human cancer, a satisfactory effect could be seen only with acute lymphoblastic leukaemia^3–5, but many investigators emphasized the toxicity of L-asparaginase. An alteration of liver function^2,5–7 has been demonstrated by the finding of hepatic lipoidosis; a marked increase in bromsulphthalein retention, and in serum levels of cholesterol, triglycerides and phospholipid; a decrease in human serum proteins and the demonstration of various clotting disorders in the course of therapy. Other authors⁸ observed the total inhibition of the early wave of mitotic activity in regenerating rat liver approximately 30 h after partial hepatectomy. We decided to study the effect of L-asparaginase preparations of high specific activity on DNA synthesis in rat liver nuclei, and to determine nuclear DNA and RNA polymerase activity in rat liver under the influence of L-asparaginase.