Document Detail


Leukemia L1210 cell lines resistant to ribonucleotide reductase inhibitors.
MedLine Citation:
PMID:  3276399     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Leukemia L1210 cell lines, ED1 and ED2, were generated which were resistant to the cytotoxic effects of deoxyadenosine/erythro-9-(2-hydroxyl-3-nonyl)adenine and deoxyadenosine/erythro-9-(2-hydroxyl-3-nonyl)adenine plus 2,3-dihydro-1H-pyrazole[2,3a]imidazole/Desferal, respectively. The ED1 and ED2 were characterized to show that these cell lines had increased levels of ribonucleotide reductase as measured by CDP reduction. The reductase activity in crude cell-free extracts from the ED1 and ED2 cells was not inhibited by dATP. For CDP reductase, the activation by adenylylimido diphosphate and inhibition by dGTP and dTTP in these extracts from the ED1 and ED2 cells were the same as for the wild-type L1210 cells. The ED1 and ED2 cells were highly cross-resistant, as measured by growth inhibition, to deoxyguanosine/8-aminoguanosine, 2-fluorodeoxyadenosine, and 2-fluoroadenine arabinoside. While the ED2 cells showed resistance to 2,3-dihydro-1H-pyrazole-[2,3a]-imidazole/Desferal (6-fold), the ED1 and ED2 cell lines showed less resistance to hydroxyurea, 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone, and the dialdehyde of inosine. These data indicate that the mechanisms of resistance to the ribonucleotide reductase inhibitors are related to the increased level of ribonucleotide reductase activity and to the decreased sensitivity of the effector-binding subunit to dATP.
Authors:
J G Cory; G L Carter
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  48     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1988 Feb 
Date Detail:
Created Date:  1988-03-14     Completed Date:  1988-03-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  839-43     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, University of South Florida College of Medicine, Tampa 33612.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Deaminase / metabolism
Adenosine Kinase / metabolism
Animals
Antineoplastic Agents*
Cell Division / drug effects
Cell Line
Kinetics
Leukemia L1210 / drug therapy*,  enzymology
Mice
Nucleosides / pharmacology,  therapeutic use*
Ribonucleotide Reductases / antagonists & inhibitors*
Structure-Activity Relationship
Grant Support
ID/Acronym/Agency:
CA 27398/CA/NCI NIH HHS; CA 42070/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Nucleosides; EC 1.17.4.-/Ribonucleotide Reductases; EC 2.7.1.20/Adenosine Kinase; EC 3.5.4.4/Adenosine Deaminase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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