Activation of deoxycytidine kinase during inhibition of DNA synthesis by 2-chloro-2'-deoxyadenosine (Cladribine) in human lymphocytes.
Biochem Pharmacol
; 56(9): 1175-9, 1998 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-9802328
ABSTRACT
Deoxycytidine kinase (dCK, EC.2.7.1.74), a key enzyme in intracellular metabolism of many antileukemic drugs, was shown to be activated during treatment of lymphocytes by 2-chloro-2'-deoxyadenosine (Cl-dAdo, cladribine), a potent inhibitor of DNA synthesis. While 5-[3H]-thymidine (TdR) incorporation into DNA was decreased by 80-90%, dCK activity was doubled as a consequence of incubating the cells with 1 microM 2-chloro-2'-deoxyadenosine. Thymidine kinase (dTK, EC.2.7.1.21) activity was slightly decreased under the same conditions, similarly to 5-[3H]-thymidine incorporation. dCK activation could not be prevented by cycloheximide, and neither the amount of dCK protein nor its mRNA level was increased after 2-chloro-2'-deoxyadenosine treatment. These results suggest a post-translational activation of dCK protein during inhibition of DNA synthesis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Linfócitos
/
Cladribina
/
Desoxicitidina Quinase
/
Antineoplásicos
Limite:
Child
/
Child, preschool
/
Humans
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Hungria