Linked Life Data

6272978

Source:http://linkedlifedata.com/resource/pubmed/id/6272978

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11 Pt 1
pubmed:dateCreated
1982-2-22
pubmed:abstractText
The biochemical basis of cellular resistance to 9-beta-D-arabinofuranosyladenine (ara-A) and its natural purine derivative, deoxyadenosine, was investigated with two mutants of cultured human T-lymphoblastoid CCRF-CEM cells. One mutant that lacked deoxycytidine kinase activity, designated CEM/ara-C, retained about 10% of wild-type deoxyadenosine kinase and deoxyguanosine kinase activity each but maintained normal adenosine kinase or thymidine kinase activity. This suggested that in these human T-lymphoblastoid cells, as in other previously studied mammalian cells, deoxycytidine and purine deoxyribonucleosides are phosphorylated by the same enzyme. Despite this extensive reduction of purine nucleoside kinase activities, the cytotoxicity of ara-A or deoxyadenosine was not appreciably affected, decreasing by only 2.5- and 6-fold, respectively. A second mutant, isolated by selecting CEM/ara-C mutants that were resistant to ara-A, showed a 100-fold increase in resistance to ara-A cytotoxicity. This ara-A-resistant subline was deficient in the activities of two enzymes, deoxycytidine kinase and adenosine kinase, and showed a high degree of resistance to deoxyadenosine, adenosine, and pyrazofurin but not to pyrimidine analogs, such as 5-fluorodeoxyuridine or 5-fluorouridine. Further studies of ara-A and deoxyadenosine phosphorylation in wild-type and resistant cell lines disclosed that, although deoxycytidine kinase is the principal enzyme for their phosphorylation in vitro, their intracellular conversion to cytotoxic nucleotides depends on the joint action of deoxycytidine kinase and adenosine kinase rather than purine-specific deoxynucleoside kinase, as previously thought.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4478-83
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1981
pubmed:articleTitle
Identification of the mechanism of activation of 9-beta-D-arabinofuranosyladenine in human lymphoid cells using mutants deficient in nucleoside kinases.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't