formyl-leurosine and Carcinoma--Ehrlich-Tumor

Some of the vinca alkaloids are well known and widely used in clinical practice, in spite of their numerous side-effects. For the elimination of untoward side-effects semi-synthetic alkaloids have been produced. This work reports on N-formylleurosine (N-F-Leu), one of these agents. Its antitumour activity is, in many respects, similar to that of other, presently used vinca alkaloids; it causes metaphase block, the appearance of multinucleated cells and polyploidization. In addition to these effects, N-F-Leu induces significant new phenomena, namely, changes in the activity of thymidine kinase, a key enzyme of DNA synthesis as well as in thymidine incorporation, and reduces the proportion of cells in S phase in a relatively short period of time after treatment: 24-29 hr. Based on these observations, the reevaluation of the mechanism of action of vinca alkaloids has become possible.

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cell Survival; DNA, Neoplasm; Mice; Mitosis; Thymidine; Thymidine Kinase; Vinca Alkaloids