The effect of N-formylleurosine on DNA synthesis of Ehrlich ascites 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.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism; D014748:Vinca Alkaloids / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D014748:Vinca Alkaloids; C016463:formyl-leurosine; D013937:Thymidine Kinase; D013936:Thymidine