A novel effect of the new antileukemic drug, 2-chloro-2'-deoxyadenosine, in human lymphocytes.
2-chloro-2'-deoxyadenosine (Cl-dAdo) is a potent drug against hairy cell leukemia and other lymphomas. Its effects on the metabolism of labeled deoxycytidine (5-[3H]dCyd) and deoxythymidine ([3H]dThd) were investigated in short term cultures of human lymphocytes. In the presence of Cl-dAdo, a more pronounced inhibition of DNA synthesis was found, accompanied with a much higher accumulation of radioactivity in dTTP than in dCTP. This difference disappeared in the presence of exogenous dThd. Analysis of intracellular metabolites of 5-[3H]dCyd showed an increase in [3H]dCTP used for liponucleotide biosynthesis and a decrease in [3H]dUMP formation in the presence of Cl-dAdo, suggesting the possible inhibition of dCMP deaminase.
Sasvári-Székely
M
M
1st Inst. Biochem., Semmelweis Med. Univ., Budapest, Hungary.
Piróth
Z
Z
Kazimierczuk
Z
Z
Staub
M
M
D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D017338:Cladribine / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis*; D003841:Deoxycytidine / Q000378:metabolism*; D003845:Deoxycytosine Nucleotides / Q000378:metabolism; D003856:Deoxyuracil Nucleotides / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014066:Palatine Tonsil; D013936:Thymidine / Q000378:metabolism*; D013942:Thymine Nucleotides / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D003845:Deoxycytosine Nucleotides; D003856:Deoxyuracil Nucleotides; D013942:Thymine Nucleotides; D003841:Deoxycytidine; D014316:Tritium; C024107:2'-deoxycytidine 5'-triphosphate; D017338:Cladribine; D004247:DNA; C007267:2'-deoxyuridylic acid; C024157:thymidine 5'-triphosphate; D013936:Thymidine