Abstract

5-Azacytidine (NSC-102 816) was prepared synthetically and independently isolated from the culture filtrate of Streptoverticillium ladakanus. It is an s-triazine analogue of cytidine possessing a broad spectrum of biological effects. In mammalian tissueit is phosphorylated to 5-azacytidine 5-phosphates and incorporated into different species of RNAs and into DNA. 5-Azacytidine 5-monophosphate inhibits orotidine 5-phosphate decarboxylase blocking thus the de novo pyrimidine synthesis. Following the administration of 5-azacytidine a rapid breakdown of liver polyribosomes has been observed; furthermore, in different systems a profound inhibitory effect of the drug on the maturation of ribosomal RNA has been found. 5-Azacytidine interferes with different induced liver enzymes; in some cases their activity is elevated since the rate of enzyme degradation is decreased. The cytostatic effect of the drug is directed primarily against lymphatic leukemia although some recent reports indicate its action also against human solid tumours. Chemotherapy of leukemic mice by 5-azacytidine results simultaneously in the depressed synthesis of liver and spleen polyamines. 5-Azacytidine exhibits furthermutagenic, abortive, immunosuppressive, antimitotic, radioprotective and virostatic effects. The drug also affects DNA and protein synthesis in embryonic tissues, cells intissue culture, regenerating livers, in bacteria and phages. The changes associated with the emergence of resistance towards 5-azacytidine are associated with the decreased activity of uridine kinase in mouse leukemia cells. On the contrary, in adult rate livers5-azacytidine administration leads to the increased activity of this enzyme. Differentauthors have used 5-azacytidine as a tool for the study of biochemical mechanisms connected with a cell proliferation and division.