Linked Life Data

7248971

Source:http://linkedlifedata.com/resource/pubmed/id/7248971

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1981-9-25
pubmed:abstractText
2-azido-2'-deoxyarabinofuranosylcytosine (Cytarazid), recently synthesized, was found to inhibit the in vitro growth of several human cell lines by 50% at concentrations ranging from 0.06 to 0.2 microM and to prevent the replication of herpes simplex virus types 1 and 2 by 98% at 50 microM. As determined with HeLa cells, the inhibition of cell growth was partially prevented by 2'-deoxycytidine (dCyd) and cytidine but not by uridine or thymidine. Cytarazid proved resistant to deamination by human cytidine/dCyd deaminases purified from acute myelocytic leukemia blast cells and from liver, a property reflected in the inability of tetrahydrouridine to enhance the cytotoxicity of the compound. Cytarazid served as a substrate for cytoplasmic dCyd kinase partially purified from human peripheral chronic lymphocytic leukemia blast cells. At a concentration of 0.4 mM, the nucleoside analog was phosphorylated 2.6 times more effectively by this enzyme than was dCyd, the Km for Cytarazid being 250 microM. In intact HeLa cells, the triphosphate derivative of Cytarazid was the major drug metabolite formed. In these cells, the analog interfered with the incorporation of radiolabeled thymidine into DNA at a concentration and a time interval at which the incorporation of uridine into RNA and amino acids into protein was not inhibited, suggesting that interference with DNA synthesis is a primary drug effect. Further analysis showed that Cytarazid triphosphate interferes with DNA synthesis in intact HeLa cell nuclei and that it inhibits both the alpha- and beta-DNA polymerases purified from HeLa cells in a manner competitive with deoxycytidine triphosphate, with Ki's of 0.6 and 0.7 microM, respectively. Cytarazid triphosphate was not able to replace deoxycytidine triphosphate for the synthesis of DNA in either intact nuclei or in cell-free preparations; but, in the cell-free assay system, the compound was found to interfere with primer-template activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3144-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1981
pubmed:articleTitle
Biological and biochemical effects of 2'-azido-2'-deoxyarabinofuranosylcytosine on human tumor cells in vitro.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.