[Directed chemotherapy of neoplastic diseases. Significance of the purine-de novo synthesis and cyclic AMP in normal and leukemic leukocytes].

Studies on purine de novo-synthesis and cyclic AMP in normal and pathologic leukocytes. The destruction of neoplastic cells by cytostatic agents depends on the existence of metabolic reactions within the cells which can be specifically blocked by these agents. Concerning the action of purine antagonists there is, as yet, no clear evidence whether de novo synthesis of purines takes place in normal as well as in leukemic leukocytes. Therefore studies were performed to evaluate the capacity of these cells to incorporate the purine precursor, glycine, into their acid-soluble adenine nucleotides. The results demonstrate that "resting" human lymphocytes are not capable of building purines de novo. However, stimulation of the cells with a mitogen (Phytohemagglutinin) leads to the induction of de novo purine synthesis. Leukemic cells do not show uniform behaviour. In order to get more information about the mechanisms by which synthesis of purines as well as the morphologic transformation of lymphocytes may be induced, the metabolism of cyclic AMP was investigated. According to our results the nucleotide does not play an essential role in initiating the transformation process, but it seems to have regulating function in the further development of cell transformation. The studies furthermore indicate an important role of cyclic AMP during proliferation of leukemic cells.