Impaired transport as a mechanism of resistance to thiopurines in human T-lymphoblastic leukemia cells.
Nucleosides Nucleotides Nucleic Acids
; 25(9-11): 1039-44, 2006.
Article
em En
| MEDLINE
| ID: mdl-17065061
ABSTRACT
In order to better understand the mechanisms of resistance to thiopurines, we studied two sublines of the MOLT4 T-lymphoblastic leukemia cell line, resistant to 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We found that the underlying mechanism of resistance in both resistant cell lines was a markedly reduction in initial transport of 6-MP (3- and 5-fold, respectively, in 6-MP- and 6-TG-resistant cells). No significant alteration of activities of hypoxanthine-guanine phosphoribosyl transferase, thiopurine methyltransferase or inosine monophosphate dehydrogenase, the key enzymes involved in the metabolism of thiopurines was detected. We conclude that defected initial transport of thiopurines by cells may very well explain their resistance to these drugs.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia-Linfoma de Células T do Adulto
/
Regulação Enzimológica da Expressão Gênica
/
Regulação Neoplásica da Expressão Gênica
/
Resistencia a Medicamentos Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Nucleosides Nucleotides Nucleic Acids
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Suécia